July 2012 Vol. 16 • No. 7 A monthly international biotechnology publication

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KH Biotech Services is an imprint of World Scientific Publishing Co. Pte. Ltd. MICA (P) 194/04/2012. © KH Biotech Services

Umbilical Cord BloodGrowing Cord Blood Cells for Cancer Patients

Umbilical Cord Blood Transplantation in Adults - The Debate between One vs. Two Units

Stem Cells in Umbilical Cord

Cord Blood Banking - To Go Public or Stay Private

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CONTENTSEDITORIAL

BIOBOARD

INDIA

6 A novel form of gene regulation in bacteria

8 Algal biofuels are no energy panacea

JAPAN

9 Medical Data Vision enhances the quality of medical care with Actian Vectorwise

SINGAPORE

10 Singapore heart surgeon to receive honour from The Royal College of Surgeons of Edinburgh

11 ELGA® to deliver innovative water purification at new Singapore General Hospital expansion

AUSTRALIA

12 Specialised Therapeutics Australia: New drug to fight hospital superbug infection

13 Group of genes hold the clue in migraine cases

14 CT scans can triple risk of brain cancer, leukemia

BRAZIL

15 Science can do more for sustainable development

MIDDLE EAST

16 Particles and persecution: why we should care about Iranian physicists

EUROPE

17 Medicyte coordinates EU-funded collaboration on Biomimetic Bioartificial Liver

18 Selvita and Orion Pharma achieve a research milestone in Alzheimer’s Disease Program

19 Zinforo (ceftaroline fosamil) receives positive CHMP opinion in the European Union for the treatment of patients with serious skin infections or community acquired pneumonia

USA

20 Vein grown from girl’s own stem cells transplanted

21 Hidden vitamin in milk yields remarkable health benefits - Weill Cornell researchers show tiny vitamin in milk, in high doses, makes mice leaner, faster and stronger

22 New report finds biotechnology companies are participating in 39% of all projects in development for new medicines and technologies for neglected diseases

23 TriReme Medical receives FDA clearance for expanded matrix of sizes of Chocolate PTA balloon catheter

24 New data show investigational compound dapagliflozin demonstrated significant reductions in blood sugar levels when added to sitagliptin in adults with type 2 diabetes at 24 weeks, with results maintained over 48 weeks

25 Zalicus successfully completes Phase 1 single ascending dose study with Z944 , a novel, oral T-Type Calcium Channel Blocker

25 Study provides clues to clinical trial cost savings

EYE ON CHINA 26 Yak genome provides new insights into high altitude adaptation

27 Gentris and Shanghai Institutes of Preventative Medicine expand collaboration

27 Chinese researchers identify rice gene enhancing quality, productivity

28 Quintiles opens new Center of Excellence in Dalian to support innovative drug development

29 BGI demonstrated genomic data transfer at nearly 10 gigabits per second between US and China

30 Quintiles deepens investment in China - New Quintiles China Headquarters and local lab testing solution announced

31 Beike earns AABB Accreditation for cord blood and cord tissue banking

31 Epigenomic differences between newborns and centenarians provide insight to the understanding of aging

FEATURES32 Growing Cord Blood Cells for Cancer Patients

36 Umbilical Cord Blood Transplantation in Adults - The Debate between One vs. Two Units

39 Stem Cells in Umbilical Cord

42 Cord Blood Banking - To Go Public or Stay Private

PEOPLE WATCH46 Open Source – The Future of Drug Discovery

REVIEW50 Ocular Toxoplasmosis

52 International Conference & Exhibition of the Modernization of Chinese Medicine & Health Products (ICMCM) - Annual Pivotal Event for Global Chinese Medicine Industry

Upcoming IssueAugustSingapore’s Next-Gen Researchers

INSIDE INDUSTRY54 German biotech innovator Altona Diagnostics launches BioNexus-certified regional

hub in Malaysia: ADT Biotech Sdn Bhd

55 FEI launches “Explore the Unseen” image contest in partnership with National Geographic

56 BIO applauds Representative Kaptur’s Energy Investment Act of 2012

56 Cytori to utilize Sistemic’s SistemQC™ to strengthen understanding of mechanisms & support design of Next-Generation Cell Therapies

57 Bosch packaging technology and Sartorius Stedim Biotech introduce PreVAS

57 CellCentric and ZoBio enter into partnership to develop lead compounds against epigenetic drug targets

CONFERENCE CALENDAR

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EDITORIALThe Potential of Umbilical CordThe world population is increasing and is projected to surpass 9 billion people by 2050. It is also becoming an aging one, with a projection of 2 billion people over 60 years, and almost half a billion people over 80 years of age by 2050. As we live longer, we are also increasingly prone to degenerative diseases. Alzheimer’s disease is on the rise, as are diabetes and cardiovascular disease. Human stem cell therapies are hoped to alleviate the short comings of current medicine and organ availability. As the debate rages between proponents of human embryonic stem cells, induced pluripotent stem cells (iPS cells) and adult stem cells, there is one human stem cell source that is still largely underexploited.

Umbilical cord — the connection between the mother’s placenta and the developing fetus is the richest source of primary human stem cells available. Each day over 300,000 babies are born all over the world, thus ‘delivering’ huge amounts of human stem cells. These stem cells are more primitive than their adult counterparts and appear to have a better regenerative capacity. Also, they have not yet been exposed to decades of environmental stress, as are most adults, which inexorably take a toll on the quality of the stem cells. Moreover, as these cells are highly representative of the genetic make-up of the global population, the pool of potential matched donors for each patient would be large, if all umbilical cords could be collected. Unfortunately, this is not the case as yet.

The umbilical cord supplies oxygenated and nutrient-rich blood to the fetus. Both the blood and the surrounding tissues are rich in stem cells. Similar to bone marrow, cord blood contains blood-forming stem cells, the hematopoietic stem cells (HSCs). HSC transplantation (HSCT) from cord blood is, as of now the most frequent application of cord blood.

It all began in 1989 Elaine Gluckman and colleagues reported successful hematopoietic reconstitution using cryopreserved umbilical cord blood in a child with severe Fanconi’s Anemia. Since then, cord blood has become a viable alternative to bone marrow transplantation for hematological diseases. Unlike bone marrow collection, which is not without risk and discomfort to the donor, cord blood collection is risk-free to both mother and new born. Unfortunately, many maternities still discard the umbilical cord. However, in view of increasing interest in this valuable stem cell source, and emerging exciting new findings on other stem cell types in umbilical cord, cord blood is increasingly banked by public and private banks. It is to be expected that in the near future umbilical cord will be used on a larger scale to also treat non-hematological degenerative diseases.

In addition to a relatively high content of HSCs, cord blood also contains less abundant stem cells such as the unrestricted somatic stem cells (USSCs) and endothelial precursor cells (EPCs). Both cell types can be grown out of umbilical cord blood and have been used successfully to cure non-hematological diseases such as cardio-vascular disease,

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Dr. Suzanne Kadereit is a stem cell biologist who obtained her PhD at the Pasteur Institute in Paris. She worked on umbilical cord blood immune and stem cells in the US, prior to working with human embryonic stem cells in Singapore. While in Singapore she became founding head of the Singapore stem cell bank. She is now group leader of the stem cell group and the Chair for in vitro Toxicology and Biomedicine at the University of Konstanz, developing stem cell-based assay systems from human embryonic stem cells for disease modelling and toxicological studies.

neurodegeneration, diabetes, in animal models. Similar to bone marrow, umbilical cord tissue also contains multipotent stromal cells (MSCs). These cells can be robustly differentiated into bone, tendon and cartilage. Bone marrow-derived MSCs are already used successfully in clinical settings to cure bone fractures and support hematopoietic engraftment after HSC transplantation.

In this issue, we feature articles discussing the use of cord blood in hematological applications, the banking of cord blood and the different types of stem cells contained within umbilical cord and blood. In general, stem cells in umbilical cord are more primitive than their counterpart in the adult. However, they are, similar to their adult counterparts, restricted in their capability to expand. As only a finite number of cells can be obtained with one collection, options are limited. However, in view of recent findings where cord blood cells have been successfully reprogrammed to pluripotency (so-called iPSC), and thus can be grown to potentially unlimited amounts, a future could be envisioned where cord blood cells are reprogrammed at collection to iPSC, expanded to large quantities and stored for later use as partially matched cell source for family members.

Suzanne KadereitDepartment of BiologyUniversity of Konstanz

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INDIA

A novel form of gene regulation in bacteria

B acteria: one of the most abundant and well-studied organisms. But a finding published in Nature Communications

makes one wonder: do we really know them that well? Despite bacteria being the focus of profuse research, scientists have only now discovered an entirely new form of gene regulation in the bacterium Escherichia coli. The discovery of this new system provides valuable information on bacteria which are often used as model systems to study topics ranging from cell functioning to human diseases.

Thousands of genes are encoded in our DNA. Some are ‘turned on’ or ‘turned off’ in different stages of growth. This controlled expression of genes is critical for the survival of the organism. One of the processes that regulate this expression is methylation - a step where the cell adds a methyl group

as an identifying mark to a part of its own DNA. Enzymes called methyltransferases (MTs) do this job for the cell. Once foreign DNA invades it, the cell can immediately kill unmethylated - unmarked - DNA using enzymes called restriction endonucleases. Bacterial cells, like ours, bank on this system to fight against foreign DNA.

Apart from playing a role in the bacterial immune system, methylation has other functions. MTs engage in two kinds of methylation - cytosine methylation, where the ‘C’ bases that make up DNA are methylated; and adenine methylation, where the ‘A’ bases are methylated. Scientists have found that adenine methylation regulates gene expression in bacteria, whereas cytosine methylation performs the same function in mammals. Recent studies hint that cytosine methylation might play a

greater role in gene expression in bacteria.To study this, Kahramanoglou and

her team isolated genomic DNA of E. coli at different stages of growth (refer to graph). They sequenced the DNA after treating it with a reagent called bisulfite to help them detect methylation status. To check if cytosine methylation did play a role in gene expression, they compared the methylation status of a wild strain of E. coli that had a cytosine methylation gene (W+) with the wild strain without that gene (W-). They found that a specific protein which regulates many genes in the stationary growth phase (called rpoS) while present in normal levels in the wild strain (W+), was in far higher levels in the lab strain (W-). Since the only difference between both strains was the presence of a cytosine methylation gene, the authors feel that cytosine methylation in

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the wild strain (W+) is the only factor that limited, and thus regulated gene expression in it. Previous research shows that this is the same process that regulates gene expression in complex eukaryotes - mammals.

Studies examine such nuances of cell functioning mostly at the level of a single gene or pathway. One special feature of this study is that Kahramanoglou and her colleagues examined entire genomes of E. coli. This approach gave them access to high resolution information which led them to the discovery of the role of cytosine methylation in bacterial gene regulation.

While cytosine methylation plays an important role in bacterial gene expression, it has a dangerous side too. Regions that undergo cytosine methylation are mutation hotspots. And some of these mutations can be deleterious. Regions in the bacterial DNA that undergo cytosine methylation therefore run the risk of harmful mutations. Previous research indicates that luckily, E.coli has found a way out. It produces a repair protein in the stationary phase (“very short (patch) repair” or “vsr”), which can revert such mutated regions back to normal. Yet this repair protein is found only in the stationary

phase. In phases like the exponential phase, where the repair protein is not found, how does E.coli take care of such errors?

The authors conclude from their experiments that methylation in the absence of vsr does not happen randomly. In the exponential phase where there is a possibility that occurring mutations can be deleterious, MTs methylate native DNA at a lower frequency than usual. Thus, non-methylation might prevent unnecessary mutations in E.coli in the absence of vsr.

It gets more interesting from here: not all bacteria are the same. Prior research shows for instance, that the cholera-causing bacterium Vibrio cholerae, also possesses a cytosine methylation system, but lacks the vsr repair protein across all growth phases. Mutations formed as a result remain uncorrected and could lead to subtle differences in V. cholerae’s genome. Kahramanoglou and her team analyzed the V. cholerae genome and think that ironically, this system might be helping V. cholerae evolve into dynamic genetically diverse forms. These forms could overcome resistance and better attack their hosts: humans, in this case.

While the authors are excited about their discovery, it’s still early days, says one of the authors Aswin Seshasayee, currently a principal investigator at the National Centre for Biological Sciences. “It is not quite clear how prevalent gene expression control by cytosine methylation is across bacteria,” he says. What he finds interesting is the possibility that MTs have acquired novel and central regulatory functions. “More broadly, I do wonder about a wider role for such DNA elements in the evolution of DNA methylation itself, irrespective of the kingdom of life,” Seshasayee says.

Processes like methylation, be it in E. coli or V. cholerae, seem highly context-specific. Bacteria seem to have evolved impressive strategies and counter strategies that permit them to make the best of all worlds. It’s time to think twice: one of the simplest life forms on earth may not be as simple as we take it to be. It could still be holding secrets we don’t know anything about.

Supriya Khedkar and Aathira Perinchery

Source: NCBS Research

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O f late, there is heady euphoria over ‘green’ algal biofuels that are dangled as a panacea for developing countries

such as India. While it is true that algal biofuels can contribute to a fossil fuel-free future, the promises of runaway successes are unrealistic. Scientists and policy makers need to address several critical issues that raise doubts over the sustainability of an extensive algal biofuel system. Do we need to re-learn sustainability lessons all over again in the light of first ‘green revolution’ which raised crop yields but left a trail of environment impacts?

Sustainability criteria need to be spelt out before anyone claims breakthroughs in this field. All claims need to be demonstrated on appropriate field-scale sizes; and an authenticated overall energy and resource balance established. Such a filter will make awareness, research, action and policy elements more realistic, achievable, accountable and transparent.

Algal cultivation, like crops, will need land, water, farmers, fertilizers, pesticides and weedicides.

As it is, water-deficit India can barely meets it agricultural needs — cumulative losses due to transpiration are 50-100 per cent higher than the rainfall. Producing 10 grams of algae per square meter from a water body daily will lead to a water loss of 10 liters and a conservative oil content of

Algal biofuels are no energy panacea20 per cent from the algae. So, producing a kilogram of algal oil will need 5,000 liters of water. A typical rainfed crop would function at a tenth to a fifth of this water use.

All cultivable land in India is already under crops, and wastelands suitable for algae are sparse. Large-scale, high-density algal cultivation can be done simultaneously with constantly flooded paddy crop covering 20 million hectares. The sodic wastelands of Kachch in western India offer three million hectares and the coastal shelf a similar area. With urban wastewaters amounting to 40,000 million liters per day, the equivalent of 10 million hectares of dedicated cultivable area could be reached

To produce one kilogram of algal fuel, one kilogram of naptha is needed for adequate nitrogen, tilting the energy balance to zero or negative

Learning from agricultural crops – especially paddy where nitrogen uptake efficiency is about 30 per cent – achieving high nitrogen efficiency is difficult in a short time-frame. Raised simultaneously with flooded paddy, nutrients taken up by algae could be fed back to paddy fields, after extracting oil and biomethanation of the residue. As the nitrogen is in organic form, its losses are low and the overall efficiency could be high. However, this requires intensive farm nutrient management.

In short, the problems of algal biofuel are akin to those of high-yielding agriculture. Taking the algal biofuel path would require India to double its area under cultivation, more than double its water budget and double its fertilizer use. This is unaffordable for India’s economy and environment.

Algal productivity is widely contested. Most productivity data are derived from small-scale studies, with projections ranging between 18–360 tonnes per hectare each

year. The higher values arise from feeding sugar and providing light for 18–24 hours daily to the algal system.

Algal cultivation is likely to be in open pond systems where yields are likely to be in the range of 5–10 grams per square meter daily. The perceived higher yields in sterile monocultures in laboratories are difficult to replicate in the field where a host of algae feeders and algal competitors thrive. In typical fast-growing algal ponds, nearly 30–40 per cent of the algal biomass is consumed by grazers and feeders.

Studies show that in short growth cycles of 5–10 days lipid accumulation is at best a paltry 10–15 per cent; and reaches 80 per cent in cycles beyond 30 days. It is misleading to multiply the highest lipid content of 80 per cent with the upper limit of yields of 360 tonnes per hectare per year (obtained by feeding sugar and artificial light at one to three per cent energy efficiency) to project a potential yield of 288 tonnes from every hectare each year. In the field, a potential oil yield in the range of three tonnes per hectare each year would be more realistic.

And the energy and solvent needs for oil extraction operations are still unclear. Unless very efficient processes are evolved, algal biofuel extraction would have poor energy balance.

Making algae ecologically competitive is something few understand. If we do not resolve the issues, we will end up with a system similar the current model of poorly sustainable, high-input agriculture, something that we don’t need and would like to avoid

Hoysall Chanakya, Centre for Sustainable Technologies,

Indian Institute of Science, Bangalore.Source: SciDev.Net

Algal biofuels, like crops, demand land, water, fertilisers, pesticides and inputs that are costly for India, says Hoysall Chanakya.

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J apanese medical software and service provider chooses Vectorwise in under one week following rigorous evaluation

of database solutions Actian Corporation announced that

Medical Data Vision, a medical software and service provider to Japanese hospitals and healthcare providers, has selected the record-breaking analytical database, Vectorwise, to power their Evidence Based Medicine service.

“The Japanese health care system is constantly recognized as one of the best in the world”

Founded in Tokyo, Japan, Medical Data Vision develops and sells management support software designed for hospitals and other healthcare providers including Evidence Based Medicine (EBM) service. EBM aims to improve the quality of medical care by analyzing and sharing the medical results using clinical data, epidemiological studies, market research and drug development. EBM service can collect large volumes of data which can slow query performance. With the aid of their partners Cyber Systems, Medical Data Vision selected the Vectorwise analytical database to enable their EBM service to deliver faster results on large volumes of medical data.

“We needed a high performance database for our Evidence Based Medicine (EBM) service which analyzes medical data gathered from hospitals,” said Shinji Hirai, Business Development Division of Medical Data Vision. “Over a period of 2 months, we evaluated 5 other high performance database options and only discovered Vectorwise in the last week of testing. At first we were doubtful of the claims citing analytical speeds of 70-100x faster, but our own testing confirmed these astonishing results. We tested and selected Vectorwise in the last week of our evaluation period based on outstanding high performance and affordability. We are very grateful of what Vectorwise enables us to achieve; now we can deliver faster analytical insights on our large and complex volumes of medical data.”

JAPAN

Medical Data Vision enhances the quality of medical care with Actian Vectorwise

The record-breaking Vectorwise database last year smashed the Transaction Processing Performance Council’s TPC-H benchmark by the largest margin ever recorded for 100GB, 300GB and 1TB on a single server.

“The top criteria Medical Data Vision gave us was fast performance for complex reports from big medical data,” said Masashi Ono, Director of Cyber Systems. “It also had to use commodity hardware and be easy to use and maintain. We evaluated databases on virtual environments on Amazon EC2 by running various SQL queries on high volumes of real medical data. Vectorwise delivered far superior performance.”

Insight Technology, providing database related software, service and appliance

has recently joined the project for local Vectorwise implementation and support. The new EBM service will start this summer and will contribute to the enhancement of medical quality in Japan.

“The Japanese health care system is constantly recognized as one of the best in the world,” said Jason Leonidas, Vice President of Sales and Services for Actian in Asia Pacific & Japan. “It is exciting to see Medical Data Vision use Vectorwise to enable medical practitioners to share and analyze empirical rich medical data faster. We would like to thank our Japanese distributor New Systems Technology (NST) and their partner Insight Technology for helping MDV get started with Vectorwise in under a week.”

Source: Business Wire

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T he Royal Col lege of Surgeons of Edinburgh is to recognize the achievements of a leading inter-

national cardiothoracic surgeon from the National University Hospital of Singapore at a diploma ceremony being held at the 500-year-old Edinburgh College.

Professor Chuen Neng Lee is to be awarded The Royal College of Surgeons of Edinburgh (RCSEd) International Medal in recognition of his contribution to the field of cardiothoracic surgery in the Middle East.

The President of The Royal College of Surgeons of Edinburgh, Mr. David Tolley said:

“The Royal College of Surgeons of Edinburgh is delighted to welcome Professor Lee to receive the College’s International Medal. He has been instrumental in establishing along with RCSEd an Asian Update Course in Cardiothoracic Surgery. This course is in its fifth year and follows the tripartite intercollegiate Fellowship in

SINGAPORE

Singapore heart surgeon to receive honour from The Royal College of Surgeons of Edinburgh

Cardiothoracic Surgery held in Hong Kong and Singapore. His role in establishing this examination cannot be underestimated and he has been keen to promote quality assessment in both this exam and other exams with the College in Singapore.

“RCSEd has a long history of innovation and Professor Lee’s contribution exemplifies this quality. I take great pleasure in presenting his International Medal to marks his outstanding contributions in advancing the field of surgery.”

Established in 1505, and with a worldwide membership, The Royal College of Surgeons of Edinburgh is one of the world’s oldest and largest surgical establishments dedicated to the pursuit of excellence and advancement in surgical and dental practice, through its activities in education, training and examinations.

At the diploma ceremony, Professor Lee will join surgeons worldwide who

have travelled to Edinburgh to receive Fellowship and Membership diplomas in recognition of their success in achieving the required standards of the rigorous surgical examinations.

Commenting on receiv ing the International Medal from the College, Professor Lee said:

““It is a great honour to be awarded this college medal. Over the years of working with surgeons from the Royal College of Surgeons of Edinburgh, I discovered that this is a group of very serious professionals, dedicating their life’s work to education and training at the highest level. They truly represent the ideals of the College and deserve the deepest respect.

“My colleagues in Singapore and Hong Kong admire them tremendously. The reputation of RCSEd continues to be extremely high in the Far East. We look forward to continuing to work together to educate our future generations of surgeons.”

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E LGA LabWater, global laboratory water brand of Veolia Water Solutions & Technologies, the world’s leading

water technology and service company has been awarded the contract to supply and install an ultra-pure water production system and innovative duplex distribution loop over 2 buildings and 6 different floors for the new Singapore General Hospital (SGH) expansion.

The Singapore General Hospital was established in 1821 and is Singapore’s oldest and largest tertiary acute hospital with more than 1,500 beds and 8,200 employees. A new

ELGA will provide CENTRA® and MEDICA® systems for SGH’s new wing.

ELGA® to deliver innovative water purification at new Singapore General Hospital expansion

expansion project includes a new building which will host the Pathology, Research and Biochemistry departments of SGH.

Supplying the main contractor, Taikisha, Veolia Water Solutions & Technologies Singapore in collaboration with Chemoscience will install 12 CENTRA® and 4 MEDICA® units across the 13-storey building. The innovative solution delivers consistent purified water ensuring uptime for critical services such as pathology. Veolia will also provide a professional service to ensure the performance of the entire life of

the system with experts in-house and field service support.

“By leveraging on the strong capabilities of the Veolia local team and the global expertise of ELGA, we offered a customized and greener solution to SGH allowing reduced water consumption. This new project reinforces our position as expert in delivering smart water solutions to hospitals” said Laurent Besson, General Manager of Veolia Water Solutions & Technologies Singapore.

Completion of the expansion project is anticipated by August 2012.

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A new therapy to treat a common hospital superbug* infect ion Clostridium difficile, will soon be

available to Australian & New Zealand patients.

Melbourne b iopharmaceut ica l company Specialised Therapeutics Australia Pty, Ltd. (STA) has entered into an exclusive distribution & license agreement with US based Optimer Pharmaceuticals, Inc. (Optimer) to develop and commercialize the drug DIFICID in Australia and New Zealand.

This macrolide antibiotic therapy, taken in tablet form, is regarded as a breakthrough treatment to help fight the serious CDI, which typically develops in patients using broad-spectrum antibiotics. The organism – which is resistant to many common household and commercial disinfecting agents - targets the large intestine, causing diarrhoea. It is extremely common in hospitals and aged care facilities and can be fatal.1

A recent media report indicated 14 Victorians died from the infection during a 15-month period in 2010 and 2011.2 According to data generated by the Quebec provincial hospitalization database, there were 7004 cases of C. difficile across Quebec from April 1st 2003 to March 31st 2004, and 1270 people died after contracting CDI.3

AUSTRALIA

Specialised Therapeutics Australia: New drug to fight hospital superbug infection

STA Chief Executive Officer Mr. Carlo Montagner said: “CDI presents a serious bacterial health threat and current CDI treatment options available in Australia and New Zealand are limited. Our license of DIFICID provides a great opportunity to bring a much-needed new therapy to patients.”

DIFICID is the first in a new class of macrolide antibiotics, which are minimally absorbed by the bloodstream and have been shown to fight the CDI infection while leaving healthy gut flora untouched.4 DIFICID works by inhibiting the bacterial enzyme RNA polymerase, resulting in the death of C. difficile bacteria.4 Patients typically develop CDI when using broad spectrum antibiotics, which disrupt normal gut flora and enable the infection to take hold.

Hypervirulent strains of CDI, including PCR ribotype 027 strains recently identified in Australia, have been associated with epidemic spread and high rates of severe disease and death.5

R isk factors for CDI inc lude exposure to antimicrobial drugs, gastric acid-suppressive therapy, advanced age, prolonged hospitalization, cancer chemotherapy, co-morbidity and immuno- suppression. Although most cases have been in hospital inpatients, increasing numbers of community-associated cases are now being reported.1

A leading Australian authority on C. difficile, Professor Thomas Riley from the University of Western Australia, said data showed patients treated with DIFICID were “significantly less likely” to develop recurrent infections.6,7

He said new treatment options like DIFICID were highly desirable, with infection rates rising “two to three fold” in public hospitals around the country.

An application to make DIFICID widely available in Australia has been filed with the Therapeutic Goods Administration, with the drug expected to be launched by June 2013.

Optimer Chief Executive Officer Pedro Lichtinger said he looked forward to DIFICID being widely available in Australia and New Zealand. “We are committed to enabling better outcomes for patients with this difficult to treat infection. I believe this is a truly innovative therapy providing a new patient option for an unmet medical need,” he said.

DIFICID is approved by the U.S. Food and Drug Administration (FDA) for the treatment of Clostridium difficile-associated diarrhoea (CDAD) in adults 18 years of age or older. Likewise, the European Commission granted Marketing Authorisation to fidaxomicin for the treatment of adults with Clostridium difficile infections under the trade name DIFICLIR™.

* Superbug is a common reference to an organism or infection, which is resistant to multiple antibiotics.

References: 1. Cheng AC, Ferguson JK, Richards MJ, et al. Australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection. Med J Aust 2011; 194: 353-358. 2. The Age, Saturday 26 May 2012. 3. Eggertson, L. CMAJ 2004; 171: (11) 1331-1332 4. Duggan ST. Fidaxomicin: In Clostridium Difficile Infection. Drugs 2011 5. Stuart R, Marshal C. Clostridium difficile infection: a new threat on our doorstep. Med J Aust 2011; 194: 331-332 6. Louie TJ, Miller MA, Mullane KM et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection N Engl J Med 2011;364: 422-31. 7. Cornelly OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet 2012

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R esearchers have identified four new genes linked to the most common form of migraine, in a discovery that

could eventually aid in the development of treatments for the debilitating attacks.

A team of Australian and European scientists found six genetic variants among the DNA code of 4800 people who suffer from “migraine without aura”, which affects 12% of the population and accounts for more than 60% of all migraines. Four of the genes are new and two confirm previous findings.

The study, by the International Head-ache Genetics Consortium, appeared in the journal Nature Genetics.

The variants were absent among more than 7000 people who do not suffer from the debilitating headaches, which can last up to three days and cause nausea, vomiting, and sensitivity to light and sound.

The less common “migraine with aura” produces the sensation of flashing light, blind spots and tingling in the hand or face.

Studies show that 6-8% of men and 15-18% of women suffer from migraines, which are a major cause of absence from work.

Group of genes hold the clue in migraine cases

Frequent sufferers use preventive therapies such as beta blockers, antidepressants, anti-seizure drugs or Botox shots.

Although scientists do not know the precise cause of the neurovascular brain disorder, they suspect it occurs when molecules that transmit signals between brain neurons act irregularly. Two of the newly identified genes support another theory that disturbances in blood flow play a role.

“Studies of this kind are possible only through large-scale international collaboration – bringing together the wealth of data with the right expertise and resources. The identified genes open new doors to investigate how this type of migraine comes about,” said Dr Arn van den Maagdenberg, one of the senior authors on the paper.

Lyn Griffiths, the Director of the Griffith Institute of Health and Medical Research at Griffith University, said the research was compelling because it involved “a very significant number of migraine cases, it was the first focused [migraine without aura] study – an area under-researched

in terms of genetics – and it adds to our information regarding the genetic basis of migraine.

“This research has contributed to our understanding of the common forms of migraine and ultimately may aid in developing better diagnosis and treatment of migraine and its sub-types.”

Professor Griffiths, who was not involved in the international study, recently completed separate research identifying a new region on the X chromosome that also plays a part in migraine.

The research indicates that more than one X chromosomal gene may be involved, and implicates a gene that contributes to iron regulation in the brain.

Whereas females have two X chromo-somes, males have an X and a Y chromosome. “These results provide more support for the role of the X chromosome in migraine and may explain why so many more females suffer from the disorder,” Professor Griffiths said.

Justin Norrie, Editor of The Conversation

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J ust two CT (computed tomography) scans of the head in childhood can triple the risk of brain cancer in later

life, and as few as five to 10 scans can triple the risk of leukaemia, a study has found.

But an Australian expert says the risk posed by ionising radiation from the scans is well-documented, and that the study merely underscores the importance of using the technology only where strictly necessary from a clinical perspective.

The findings by researchers from the University of Newcastle in England, reported in The Lancet, were based on a study of almost 180,000 patients who had CT scans between 1985 and 2002 at 70% of hospitals in Britain.

The absolute risk of developing the cancers remains small. For every 10,000 people under the age of 20 who receive 10 milligray from a CT scan, there will be one excess case of leukaemia, the researchers said. One additional brain tumour can be

CT scans can triple risk of brain cancer, leukemiaexpected for every 30,000 who receive the same dose.

Use of CT scanning has increased drastically in the past 10 years, particularly in the United States, the team said. CT scans – a major advancement of 20th-century medicine – allow doctors to glean a much clearer picture of what is happening inside the body than conventional X-rays. But they also use a much higher dose of radiation. Calculations based on data from survivors of the atomic bomb attacks in Japan have been used by some scientists to suggest that CT scans could increase the risk of cancer in children.

Bruce Armstrong, a Professor of Public Health in the Sydney School of Public Health at the University of Sydney, said that “material increases in risk of brain tumour and leukaemia in younger people exposed to higher accumulated levels of ionising radiation from CT imaging are not unexpected and entirely consistent

with what has been known for a long time about the cancer causing effects of ionising radiation.

“This work emphasizes the very great importance of only using this form of imaging when it has a strong medical justification and in doing so in ways that minimize the amount to which the patient who is being imaged is exposed to the radiation needed to produce the required images.”

Study leader Mark Pearce, from the University of Newcastle’s Institute of Health and Society, called for further refinements to allow reduction in CT doses. This “should be a priority, not only for the radiology community, but also for manufacturers.

“Alternative diagnostic procedures that do not involve ionising radiation exposure, such as ultrasound and MRI (magnetic resonance imaging) might be appropriate in some clinical settings.”

Justin Norrie, Editor of The Conversation

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T he message from Rio+20 is for practical action to deliver existing targets. Scientists must identify and

overcome barriers to change. Sha Zukang, secretary-general of

Rio+20, held a press conference in Rio de Janeiro, heralding the start of the final phase of negotiations at the UN Conference on Sustainable Development. He stressed that this meeting is fundamentally different to the first Earth Summit, held in Rio in 1992.

Twenty years ago, the meeting produced a legally binding document including conventions on biodiversity, desertification and, ultimately, climate change. The Rio+20 outcome agreement, to be negotiated next week, has no basis in law, said Sha — it is voluntary and political, and its goal is practical action.

Indeed, the agreement will seek commitment to deliver on what had previously been agreed in 1992 — a long list of largely unattained targets.

This is a meeting born out of gloom that so little has been achieved, as shown by the UN Environment Programme’s GEO-5 report launched last week. The question is, can the science, technology and innovation (ST&I) communities deliver yet more to further the cause of sustainable development and avert some of the environmental crises they have predicted?

Science has its own barriers - in some ways it is hard to see what else they can do, as ST&I seems to have several intractable issues of its own.

Scientists concerned about global change complain repeatedly that a fault in their community is the ‘silo mentality’. This behaviour is thought to undermine the potential of science to deliver solutions, which is why there has been a revamp of the CGIAR agricultural research programmes and the formal launch of the immense enterprise of Future Earth this week.

There is undoubtedly a lot of truth in this. But it is also true that many scientists are driven by in-depth understanding in their area of research. Forcing them to behave differently — for example to contribute to Sha’s call for practical solutions rather than

BRAZIL

Science can do more for sustainable developmentexploring why things happen — goes against that drive.

Another barrier to the further contribution of the ST&I community to sustainable development is that implementation of their discoveries and inventions is often beyond their expertise.

Implementing ideas without taking into account the wider context, runs into the problem that life is interconnected and messy, as we are increasingly told in reports such as People and Planet or The European Review of Development. An intervention, such as the conversion of a food crop field to a biofuel plantation, has effects on water resources and food security, which can go far beyond the original attempt to improve energy availability.

Finally, there seem to be limitations to the extent to which scientists can communicate with policymakers and interest groups about the state of the planet.

Scientists do deserve credit for keeping alive — over the past year — a fear of the consequences of inaction at Rio+20. But there is a limit to the extent to which the facts can galvanize practical action when they have to compete for attention with ideology, international relations, national sentiment and lobbyists pursuing single (though sometimes worthwhile) causes.

There are 20,000 members of civil society registered for the Rio+20 conference. Scientists cannot make full use of the same PR techniques of these other groups without undermining their core selling point — their reputation for independence.

Agenda for practical action - but there are ways round these obstacles. Research funders who pursue multidisciplinary, collaborative, global research agendas must acknowledge that they need to seek a new type of scientist to carry it out — one with a mentality and training that fits the new scientific order of problem-based research.

Furthermore, the links that natural scientists are pursuing with social scientists, to establish new types of research programme, should be pushed to a more radical conclusion. Social scientists should be put in charge of research programmes

rather than just invited in as collaborators. To tackle the problem of applying neat

solutions in a messy world, those working in ST&I need to try to work with human nature, not against it. Instead of making naïve calls for changes in values or behaviour — as some scientists did at the Planet Under Pressure meeting and previously — they need to work with things as they are.

That is why grassroots innovation has so much potential — because it harnesses human ingenuity where resources are limited. Similarly, the desire to own devices such as mobile phones, six billion of which are now in use around the world, needs to be exploited, and the broadband divide needs to be tackled to develop innovation for sustainable development.

Finally, despite the limits that scientists have found in trying to galvanize action through presenting the data, there is still a lot to be done regarding communication.

Multidisciplinary conferences should be assessed, difficult though this may be, to find out what benefits they delivered, how they should be evaluated, and how they could be improved. Planet Under Pressure was a brave attempt at just such a meeting, but some delegates said its structure stifled interaction between the disciplines and full-blooded discussion.

The cause of improving communication needs to be pursued at a local level as well. In Indonesia, scientists working with ELRHA (Enhancing Learning and Research for Humanitarian Assistance) have successfully liaised with local leaders, allowing a flow of data which has helped them develop tsunami preparation systems. This kind of approach needs to be replicated.

ST&I researchers can contribute more to realizing Sha’s practical agenda for sustainable development. But they need to recognize what science can change — and make these changes — and what it can’t. The latter they will have to leave to the expertise of someone else.

Aisling Irwin Consultant News Editor, SciDev.Net

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O n a given day, your typical physicist is mainly preoccupied with trying to understand the intimate secrets

of the universe. As with most academics, we get to visit one another in parts of the world to discuss our ideas. And as long as our curiosity continues to produce valuable contributions, we’re given the freedom and resources to pursue our academic endeavors.

That is, unless you’re a physicist in Iran. On January 12 2010, as he left for work, Professor Masoud Alimohammadi was assassinated by the blast from a motorcycle bomb detonated outside his car.

His academic research was on quantum field theory and appears to have had no professional connection with any nuclear research and development. He was just sympathetic to the views of the reformist movement in Iran.

Over the last two years a number of physicists in Iran have suffered similar fates, some involved in nuclear physics research, some not. The most recent was on Sunday May 13. The journal Nature reported:

“Omid Kokabee, an Iranian graduate student who has been imprisoned in Tehran for the past 15 months, was sentenced to 10 years on Sunday for allegedly conspiring with foreign countries against Iran.”

Omid Kokabee faces ten years in jail for communicating with a hostile government. University of Texas

Kokabee was accused and convicted of “communicating with a hostile government” after spending time abroad at the Institute for Photonic Science in Barcelona and the University of Texas in Austin. He had already spent 15 months in prison awaiting trial. He has consistently denied all allegations and no credible evidence was presented against him during the trial. His field of work does not include nuclear physics.

Oppression in Iran is not something we’re unfamiliar with. But it could have implications for the many Iranian physics students in Australia studying in masters and PhD programs.

MIDDLE EAST

Particles and persecution: why we should care about Iranian physicists

Their reasons for studying physics are much like those of other bright young people who are deeply inquisitive. They, too, desire to understand why the world is as we see it. But unlike undergraduate physics students in Australia and abroad, there is pressure brought to bear on the best of these students to direct their efforts into very specific research areas of interest to the Iranian regime.

This might take the form of friendly approaches from government officials. Or it may take the form of “… threats to him and his family”, as Kokabee wrote before his court appearance.

The ongoing political tensions within Iran, and between Iran and the international community over its nuclear intentions, have a direct consequence for Iranian physics students, at home and abroad.

Many physics students pursue their graduate studies abroad. For Iranian students, this takes on an additional imperative: it is one way for talented Iranian students who are uncomfortable with the political climate in their home country to leave.

There are obvious benefits to the student, as they develop advanced skills in their chosen discipline. But there are also broader benefits to the host university and nation, as they gain access to excellent students who contribute to their research programs and intellectual capital.

Visiting students are also exposed to our political system, warts and all (where rule of law means that it is important, for instance, how our elected representatives spend tax-payers’ or union-members’ money). One might hope that some of these highly capable students do eventually return to Iran, and find themselves in a position to positively influence the future direction of their home country.

In Australia, this possibility is under some threat, through the Autonomous Sanctions Act (2011) which, among other things, restricts enrolment in courses that involve study in nuclear sciences,

ballistic missiles, avionics and other military activities. It is difficult to get student visas for Iranians whose proposed graduate research would involve potentially security-sensitive equipment or training. This includes things like moderately high power lasers common to many physics departments.

There is certainly cause to be concerned about the transfer of sensitive skills to the Iranian regime. However, there is also growing wariness on the part of Australian universities to accept Iranian students into their graduate programs due to difficulties in obtaining student visas, and fears of the potential risk of inadvertently breaching the Autonomous Sanctions Act.

Balancing the potential security concerns with the diplomatic, cultural and intellectual benefits of accepting Iranian students to Australia is a question for the Department of Foreign Affairs and Trade to resolve with Australia’s various security agencies.

But let’s not forget the plight of Mr. Kokabee and other Iranian physicists, whose lives and liberties are curtailed because of their scientific curiosity.

Thomas Stace, University of Queensland

Peter Rohde, Macquarie University Source: The Conversation

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R esearch is receiving 4.2 Mio Euros from the European Union Seventh Framework Programme.

Medicyte, The Electrospinning Com-pany and the Universities of Manchester and Pisa launch a European wide unique project with the aim to design a biomimetic bioartificial liver (Re-Liver). The company GABO:mi ensures professional project management.

Within the European Union, 6% of the population is suffering from chronic liver diseases. And although the liver is one of the best-studied organs in the human body, therapeutic approaches are often precluded. The scientists experienced several limitations for possible applications. On the one hand, suitable donor livers for solid organ transplant are in short supply and on the other hand, in-vitro and ex-vivo technologies for recapitulating liver function still fall short of reliability, consistency, and predictability.

The aim of Re-Liver is to reconstitute a standardized and reproducible bioartificial liver organoid (BLO) using healthy human liver as an architectural and biomaterial template. According to the EMA criteria, the BLO is a cell-based medicinal product, a highly innovative and complex medicine. In addition to the Advanced Therapy Medicinal Product (ATMP), new diagnostic tools and further products in cell-based applications will be developed and validated by the Re-Liver Consortium, made up of three industrial partners, all SMEs, focusing the commercialization of market-leading products across Europe and further afield. The results of Re-Liver could be used for minimal invasive implantation to treat metabolic diseases, such as Haemophilia A, minimizing the transition from concept to clinic, and finally as an alternative for solid organ transplantation - giving new hope to over 10,000 people waiting for a liver transplant in the EU.

Dr. Joris Braspenning, CEO and CSO of Medicyte GmbH, Coordinator of the Re-Liver consortium comments: “I am highly delighted receiving the opportunity from

EUROPE

Medicyte coordinates EU-funded collaboration on Biomimetic Bioartificial Liver

the European Union to lead the Re-Liver joined forces of industry and academia. The combination of our complimentary areas of expertise will give a deeper insight into the complex bioartificial liver design, but is also an innovative approach to develop better and quicker diagnostic tools and cell-based products. This will be of great benefit for tomorrow’s Advanced Therapies

and of course for patients suffering from liver diseases.”

This research is receiving funding (4.2 Mio Euros) from the European Union Seventh Framework Programme (FP7/ 2007-2013) under grant agreement n° 304961

More information soon on the Re-Liver project page: www.reliver.eu

Source: B3C newswire

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S elvita S.A., a biotechnology company from Krakow, Poland announced that its collaboration with Orion

Corporation from Espoo, Finland on SEL103 program, for the symptomatic treatment of Alzheimer’s disease has reached the main research milestone and that the jointly discovered molecules from two different chemical families will progress into further pre-clinical characterization before the selection of a candidate into development.

The companies entered into a global collaboration with the aim to discover, develop and commercialize SEL103, Selvita’s proprietary program for the treatment of Alzheimer’s disease and other cognitive disorders in 2010. Selvita is responsible for early research on the program and

Selvita and Orion Pharma achieve a research milestone in Alzheimer’s Disease Program

Orion will take over the pre-clinical and clinical development as well as further commercialization.

Under the terms of the agreement, Selvita is responsible for the discovery and Orion is responsible for the development and global commercialization.

“The joint project with Orion and Selvita has been proceeding very well despite of many challenges in the biology. I have enjoyed working with the open minded, enthusiastic, and goal-oriented team of Selvita that has been able to meet the pre-agreed deliverables of the project. Especially, Selvita’s medicinal chemistry design and synthesis people have even exceeded the high expectations we had in the start. While practical work is now gradually switching

from Selvita to Orion’s responsibility I look forward to seeing confirmatory preclinical study results that would qualify compound(s) to be selected for further development and clinical studies” said Dr. Jukka Sallinen, Head of CNS Research of Orion.

“We a r e de l i gh t ed w i th t he research progress in SEL103” said Pawel Przewiezlikowski, the Chief Executive Officer of Selvita, “The milestone with Orion is the first publicly announced milestone from Selvita integrated research collaborations and another proof of the skills of Selvita scientific team. We look forward to the further development of the program by Orion”.

Source: B3C newswire

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A straZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) has adopted

a positive opinion, recommending the approval of Zinforo (ceftaroline fosamil), a new intravenous cephalosporin antibiotic for the treatment of adult patients with complicated Skin and Soft Tissue Infections (cSSTI) or Community Acquired Pneumonia (CAP). The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union.

Ceftaroline fosamil is the first monotherapy antibiotic to combine the established tolerability of the cephalosporin class, with effective coverage of a range of bacteria responsible for serious skin infections and pneumonia, including difficult to treat strains such as methicillin-resistant Staphylococcus aureus (MRSA) in cSSTI and Streptococcus pneumoniae in CAP.

The CHMP reviewed data from the Phase III clinical trial programmes which included four pivotal registration trials, CANVAS 1 and 2 (cSSTI) and FOCUS 1 and 2 (CAP). Clinical data demonstrated that Zinforo was effective and well tolerated in adult patients (≥18 years of age) with cSSTI or CAP, including those patients with underlying co-morbidities.

Zinforo (ceftaroline fosamil) receives positive CHMP opinion in the European Union for the treatment of patients with serious skin infections or community acquired pneumonia

cSSTI and CAP are infections commonly associated with considerable morbidity and mortality, and represent a major challenge to health care systems. cSSTIs are estimated to cause over 1.3 million hospitalizations per year in Europe. Similarly, approximately one million people are hospitalized in Europe each year with CAP.

“ We a r e p l e a s e d w i t h t h i s recommendation for Zinforo, which we believe may make a valuable contribution in the fight against drug-resistant infection,” said Martin Mackay, President, R&D, AstraZeneca. “We remain one of the few companies still committed to novel antibiotic research, with one of the world’s largest antibacterial pipelines and many strong partnerships to address this significant unmet medical need.”

In 2009, Forest Laboratories granted AstraZeneca exclusive worldwide commercial rights and co-exclusive development rights for ceftaroline fosamil, excluding US, Canada and Japan. Forest launched ceftaroline fosamil with similar indications under the trade name Teflaro® in the US in March 2011.

“The CHMP positive opinion to recommend approval of Zinforo is an important step in bringing to the global market new treatment options for patients suffering from serious bacterial infections,

particularly in view of increasing resistance,” said Marco Taglietti, MD, President Forest Research Institute.

AstraZeneca has made regulatory submissions in a number of countries where it has commercialization rights and further submissions are planned in 2012.

About cSSTI and CAP:Complicated Skin and Soft tissue

Infections (cSSTI) are difficult-to-treat infections of the skin and underlying soft tissues such as fascia and muscle layers e.g. deep soft tissue abscesses, cellulitis and surgical site infections. cSSTIs are among the most common antibiotic treated infections in the hospital setting and represent approximately 12% of all antibiotic-treated hospital patients in Europe.

Community Acquired Pneumonia (CAP) is an acute infection of the lungs in a patient who has not been exposed to a hospital or long-term care facility. The estimated incidence of CAP is between two and 12 cases per 1000 inhabitants in Europe each year. The annual incidence of CAP in the elderly has been estimated to be four-times that of younger populations, and with an expected 30% of the European population reaching ‘elderly’ status by 2060, the burden of CAP will be even more significant in the coming years.

CAP and cSSTI can be associated with morbidity, mortality, resource use and healthcare costs and despite the availability of a variety of antibiotics to treat CAP and cSSTI, studies show that many patients do not receive effective first-line empiric treatment.

In addition, emerging antimicrobial resistance is a global concern.

Across Europe, methicillin-resistant Staphylococcus aureus (MRSA), the most common cause of cSSTI, affects 150,000 patients per year, resulting in attributable extra in-hospital costs of 380 million.

T h e E u r o p e a n A n t i m i c r o b i a l Resistance Surveillance Network report that in Streptococcus pneumoniae, the most common cause of CAP, 25-50% of isolates are non-susceptible to penicillin (PNSP).

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F or the first time doctors have successfully transplanted a vein grown with a patient’s own stem cells,

another example of scientists producing human body parts in the lab.

In this case, the patient was a 10-year-old girl in Sweden who was suffering from a severe vein blockage to her liver. The girl’s doctors decided to make her a new blood vessel to bypass the blocked vein instead of using one of her own or considering a liver transplant.

They took a 9-centimetre section of vein from a deceased donor, which was stripped of all its cells, leaving just a hollow tube. Using stem cells from the girl’s bone marrow, scientists grew millions of cells to cover the vein, a process that took about two weeks. The new blood vessel was then transplanted into the patient.

Because the procedure used her own cells, the girl did not have to take any drugs to stop her immune system from attacking the new vein, as is usually the case in transplants involving donor tissue.

“This is the future for tissue engineering, where we can make tailor-made organs for patients,” said Suchitra Sumitran-Holgersson

USA

Vein grown from girl’s own stem cells transplanted

of the University of Gothenburg, one of the study’s authors.

She and colleagues published the results of their work online Thursday in the British medical journal Lancet. The work was paid for by the Swedish government.

The science is still preliminary and one year after the vein was transplanted, it needed to be replaced with another lab-grown vein when doctors noticed the blood flow had dropped. Experts from University College London raised questions in an accompanying commentary about how cost-effective the procedure might be, citing “acute pressures” on health systems that might make these treatments impractical for many patients.

Sumitran-Holgersson estimated the cost at between $6,000 and $10,000.

Similar methods have already been used to make new windpipes and urethras for patients. Doctors in Poland have also made blood vessels grown from donated skin cells for dialysis patients.

Patients with the girl’s condition are usually treated with a vein transplant from their own leg, a donated vein, or a liver transplant. Those options can be complicated

in children and using a donated vein or liver also requires taking anti-rejection medicines.

Since her first transplant, the girl has grown 6 centimeters and gained weight. Her parents say she is much more focused, articulate and physically active, Sumitran-Holgersson said. The girl was not identified.

“She was always tired and hardly went to school before,” Sumitran-Holgersson said. “Last week, her father said she did somersaults for the first time.”

Other experts predicted it should soon be possible for doctors to build things like blood vessels and arteries for patients.

“For simple structures like veins, this technology is definitely feasible,” said Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest Baptist Medical Center. He was not part of the Lancet study. “This is a strategy that shows blood vessels can be engineered and then used anywhere in the body.”

Atala said lab-made veins could be used for conditions including dialysis and heart surgery. However, he said patients who get such veins need to be followed for years to make sure there aren’t any serious side effects or complications.

Dr. Laura Niklason, vice-chair of anesthesiology and biomedical engineering at Yale University, said it might be more challenging to replace arteries elsewhere in the body, including near the heart, where the blood pressure is higher and the structure would be under more strain.

But she said getting organs made in laboratories was no longer science fiction. While producing complicated things like kidneys, lungs and livers might take a bit longer, other body parts — like engineered skin and cartilage — are already widely available.

There are several experiments under way for blood vessels, similar to the Lancet study.

“This type of thing is not 20 years away,” Niklason said, estimating that more patients might get lab-made vessels in about five years.

Source: The Associated Press

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A novel form of vitamin B3 found in milk in small quantities produces remarkable health benefits in mice

when high doses are administered, according to a new study conducted by researchers at Weill Cornell Medical College and the Polytechnic School in Lausanne, Switzerland.

The findings, recently reported in the June 2012 issue of the journal, Cell Metabolism, reveal that high doses of the vitamin precursor, nicotinamide riboside (NR) — a cousin of niacin — prevent obesity in mice that are fed a fatty diet, and also increase muscle performance, improve energy expenditure and prevent diabetes development, all without side effects.

The Swiss researchers, led by Dr. Johan Auwerx, performed the mouse experiments, while the ability to give the animals sufficient doses of NR was made possible by Weill Cornell Medical College researchers, who played key roles in uncovering the biological story of NR.

“This study is very important. It shows that in animals, the use of NR offers the health benefits of a low-calorie diet and exercise — without doing either one,” says Dr. Anthony Sauve, associate professor of Pharmacology at Weill Cornell Medical College.

Dr. Sauve is the pharmacologist and organic chemist who has invented a simple method for efficiently synthesizing NR in large scale. He was first to show that NR increases nicotinamide adenine dinucleotide (NAD) levels in mammalian cells. NAD is a central player in energy metabolism. He has pioneered research into the compound, and he is a leader in investigating how NAD can signal adaptation in cells and in physiology.

“The research also suggests that the effects of NR could be even broader,” Dr. Sauve says. “The bottom line is that NR improves the function of mitochondria, the cell’s energy factories. Mitochondrial decline is the hallmark of many diseases associated with aging, such as cancer and neurodegeneration, and NR supplementation boosts mitochondrial functioning.”

Hidden vitamin in milk yields remarkable health benefits - Weill Cornell researchers show tiny vitamin in milk, in high doses, makes mice leaner, faster and stronger

The Swiss researchers call NR a “hidden vitamin” that is believed to also be present in many other foods, although levels are low and difficult to measure. Nevertheless, the effects of NR on metabolism “are nothing short of astonishing.”

The study depended on a series of crucial discoveries by Dr. Sauve and his laboratory colleagues.

NR, related to niacin and other common forms of vitamin B3, was first investigated more than 60 years ago by a Stanford researcher and 1959 Nobel Laureate, Arthur Kornberg. But little more was known about its effects in mammals until Dr. Sauve discovered the effect NR had in stimulating levels of NAD in mammalian cells — work he published in 2007.

NAD allows sugars, fats, and proteins to be converted into energy. Dr. Sauve’s research provided the first evidence that NR enhances NAD levels in the mitochondria in mammalian cells in culture. These findings are published in the current study. These cell-based observations were key to the demonstration that NR could stimulate tissue NAD levels in animals, and that it could stimulate NAD-dependent sirtuins, which adapt physiology to the low calorie diets that are known to extend the lifespan of many organisms.

Dr. Sauve invented a relatively simple method for efficiently synthesizing NR in large scale so that its health benefits can be studied. This methodology, which makes it possible to make NR commercially available, was patented by Cornell’s Center for Technology Enterprise and Commercialization and subsequently licensed to ChromaDex Corporation.

The development of a means to synthesize NR in adequate quantities was crucial to the current research, and the Sauve lab provided methods and NR to make the study possible. In addition, the biological observations on the effects of NR on NAD levels in cells and on mitochondria were key to the study. Finally, the Sauve laboratory has developed state of the art

analytical methods to determine NAD levels in cells, tissues and organelles, and the laboratory provided several key metabolic measurements highlighted in the study.

“Our published scientific work has verified that NR is perhaps the most potent NAD enhancing agent ever identified,” he says. His laboratory is also widely recognized for developing an expertise in the measurement of NAD metabolism in cell tissues.

With this compound, the Swiss researchers found that mice on a high-fat diet supplemented with NR gained significantly less weight (60 percent) than mice fed the same diet without NR, even though the mice supplemented with NR ate the same amount of food as mice on the high fat diet not treated with NR. They had improved energy. They were in better shape than the untreated mice, with significantly better endurance and stronger muscles. Additionally, none of the treated mice developed diabetes, as seen in the untreated mice on the high fat diet. And when fed a normal diet, NR treated mice had improved sensitivity to insulin. The NR treated mice also showed lower cholesterol levels. All of these benefits came without toxicity.

While the new study demonstrates that high doses of NR can largely prevent the negative health consequences of a poor diet in mice, Dr. Sauve stresses that the effects of high doses of the vitamin in humans have not been evaluated. “It is important to keep in mind that the amount of NR in milk and other foods appears to be small. We don’t know what effects NR would have in humans at relatively high doses,” he says.

“Still, we have very encouraging evidence of benefits of NR and NAD augmentation in general from this animal study — and much more work to do,” he says.

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S mall- to medium-sized biotechnology companies are bringing innovation to global health, according to a

report published by BIO Ventures for Global Health (BVGH) and the Biotechnology Industry Organization (BIO). The report shows that 134 biotechnology companies are participating in neglected disease research and development, which represents participation in 39% of the 191 new drugs, vaccines, and diagnostics in development for neglected diseases such as malaria, tuberculosis, dengue fever, and others.

Partnering is an important driver for biotechnology companies. The new report, Biotechnology: Bringing Innovation to Neglected Disease Research and Development, finds that 64% of all products in development by biotechnology companies across the pipeline of drugs, vaccines, and diagnostics for neglected diseases involve partnering.

According to the report, product development partnerships (PDPs) — a unique public-private partnering mechanism created to increase biopharmaceutical participation in neglected disease R&D, government agencies, and academic institutions — are driving this biotechnology company partnering for neglected diseases. Although PDPs are the focal point of industry engagement in global health, they are the second most frequent partner to

New report finds biotechnology companies are participating in 39% of all projects in development for new medicines and technologies for neglected diseases

biotechnology companies after academia with involvement in 52% of partnered projects. When a PDP is not involved in a project, biotechnology partnerships with government agencies increase, especially for vaccines and diagnostics.

Across a l l neglected diseases , biotechnology companies work alone 36% of the time, according to the report. For tuberculosis and dengue fever, companies more frequently overcome barriers and leverage some market potential to work alone. This may be because small to medium-sized companies perceive a potential market opportunity.

“We were very pleased to see the level of the biotechnology sector’s engagement in global health research and development, as a critical source of innovation. To continue progress in addressing the unmet medical needs of the developing world, both biotechnology companies and global health groups should ramp up commitment and involvement,” says Don Joseph, CEO of BVGH. “Our new report provides specific recommendations both to biotechnology companies and neglected disease stake-holders from academia, governments, nonprofits, and foundations to increase and improve their collaborative work in neglected disease research. Accelerating solutions for these devastating diseases presents major challenges but can happen if these groups

continue and increase their work together.”While the report finds that small to

medium-sized biotechnology companies are involved in 39% of all projects for neglected disease, BIO estimates there are nearly 3,000 public and private biotechnology companies worldwide. At least 90% of these companies focus on health research and development, suggesting that the 134 biotechnology companies participating in neglected disease research and development identified in the report represent about 5% of global biotechnology companies.

“It is encouraging that small- to medium-sized biotechnology companies that lead the charge in developing life-saving medicines and technologies in the developed world are so engaged in creating new drugs, vaccines, and diagnostics for the neglected diseases primarily affecting the poor in the developing world,” says Jim Greenwood, President and CEO of BIO. “The true value of this week’s BIO International Convention is to bring together industry leaders who can share insights and engage in discussions focused on potential collaborations that could lead to scientific breakthroughs that will address these and other global challenges.”

More than 1.4 billion people are affected by neglected diseases – the majority of those affected are poor and living in developing countries. When the term “neglected” is applied to a disease, it can carry a wide range of implications. Neglected can describe the patient population affected by the disease, the scientific effort underway to understand the disease, or the extent to which new products to prevent, diagnose, and treat a disease are being pursued. Neglected can also describe a health disparity where drugs, vaccines, or diagnostics are available and in use in wealthier or developed countries, but these technologies have not been extended to poorer countries due to challenges of cost, feasibility, or political will.

Source: BIO

More than 1.4 billion people are affected by neglected diseases – the majority of those affected are poor and living in developing countries.

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TriReme Medical receives FDA clearance for expanded matrix of sizes of Chocolate PTA balloon catheter

T riReme Medical, Inc. (TMI) announced that it has received FDA clearance for an expanded matrix of sizes for its

Chocolate™ PTA balloon catheter. Chocolate™ is now approved for the percutaneous transluminal treatment of lesions in the peripheral vasculature in balloon diameters from 2.0 - 4.0mm and in balloon lengths up to 120mm.

“This latest regulatory approval broadening the available size matrix of the Chocolate™ PTA Balloon marks yet another important milestone for TriReme Medical,” said Eitan Konstantino, President and CEO of TriReme Medical Inc. “There is more to come; our goal is to provide a broad range of innovative tools to improve outcomes in patients suffering from complex vascular disease.”

“Chocolate™ has become an essential part of my routine practice for treating below

the knee lesions,” said Dr. Rajesh Dave, Chief Medical Executive and Director at Cardiac Catheterization Laboratories, Holy Spirit Cardiovascular Institute, Camp Hill, PA. “With the approval of these new sizes, I will be able to expand my use of Chocolate™ and begin to treat patients with disease in the popliteal artery where we usually prefer not to stent.”

About Chocolate™: Chocolate’s novel design incorporates a constraining structure

over a semi-compliant balloon to facilitate the formation of small modules (“pillows”). Through this advanced mechanism of action, Chocolate minimizes shear stress and allows for uniform inflation and rapid deflation. The Chocolate “pillows” can expand locally to facilitate plaque modification and are designed to lower the strain and trauma induced on the vessel wall.

Source: PRNewswire-Asia

"There is more to come; our goal is to provide a broad range of innovative tools to improve outcomes in patients suffering from complex vascular disease," said Eitan Konstantino, President and CEO of TriReme Medical Inc.

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A straZeneca and Bristol-Myers Squibb Company announced results from a Phase 3 clinical study that showed

the investigational compound dapagliflozin 10 mg demonstrated significant reductions in blood sugar levels (glycosylated hemoglobin levels, or HbA1c) compared with placebo at 24 weeks when either agent was added to existing sitagliptin therapy (with or without metformin) in adult patients with type 2 diabetes. The results were maintained over a 24-week extension and similar results were observed when the data were stratified by background therapy. The findings were presented at the 72nd American Diabetes Association (ADA) Scientific Sessions in Philadelphia, PA.

The study also demonstrated significant reductions in total body weight and fasting plasma glucose (FPG) levels in patients taking dapagliflozin added to sitagliptin (with or without metformin), with results maintained throughout the duration of the study extension.

Patients were actively questioned at each study visit for signs, symptoms or events suggestive of genital infections and urinary tract infections. These events were more frequent with the dapagliflozin treatment group compared to the placebo treatment group, and were generally mild to moderate in intensity, with most patients responding to standard treatment.

“Type 2 diabetes is a complex disease that often requires patients to take multiple treatments to control their blood sugar levels, with DPP4 inhibitors being some of the most widely prescribed therapies,” said Serge Jabbour, M.D., Division Director of Endocrinology, Thomas Jefferson University. “In this study, dapagliflozin, in addition to diet and exercise, resulted in reduced blood sugar levels when added to sitagliptin, a DPP4 inhibitor. These findings add to our understanding of the effect of dapagliflozin in combination with commonly prescribed type 2 diabetes treatments.”

New data show investigational compound dapagliflozin demonstrated significant reductions in blood sugar levels when added to sitagliptin in adults with type 2 diabetes at 24 weeks, with results maintained over 48 weeks

Dapagliflozin, an investigational oral compound, is a selective and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2), which works independently of insulin. Dapagliflozin is under joint development by Bristol-Myers Squibb and AstraZeneca, and is being investigated to evaluate its safety and efficacy in improving glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise, for once-daily use as a monotherapy and in combination with other glucose-lowering drugs. If approved, dapagliflozin would potentially be the first in the new SGLT2 inhibitor class for the treatment of type 2 diabetes, a disease where high unmet medical need exists. In a comprehensive clinical trial program of 19 studies, dapagliflozin has been studied together with diet and exercise as a monotherapy, and as an add-on therapy to commonly prescribed diabetes medications, including metformin, sulfonylurea (glimepiride), thiazolidinedione

(pioglitazone), and insulin (with or without other diabetes therapies).

In January 2012, the US Food and Drug Administration (FDA) issued a complete response letter regarding the New Drug Application (NDA) for dapagliflozin for the treatment of adults with type 2 diabetes, requesting additional clinical data to allow a better assessment of the benefit-risk profile for dapagliflozin. In April 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending the approval of dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and exercise, in combination with other glucose-lowering medicinal products including insulin, and as a monotherapy in metformin intolerant patients. The CHMP positive opinion for dapagliflozin will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union.

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BIOBOARD

P hase 1 multiple ascending dose study with Z944 to begin third quarter 2012Zalicus Inc., a biopharmaceutical

company that discovers and develops novel treatments for patients suffering from pain and immuno-inflammatory diseases, announced that it is has successfully completed a Phase 1 single ascending dose (SAD) clinical study with Z944, its novel, oral, T-type calcium channel blocker. The study results indicate that Z944 was generally well-tolerated and a maximum tolerated dose was achieved. Z944 will advance into a Phase 1 multiple ascending

Zalicus successfully completes Phase 1 single ascending dose study with Z944 , a novel, oral T-Type Calcium Channel Blocker

dose (MAD) study in the third quarter of 2012. Assuming Z944 successfully completes the MAD study, Z944 could enter Phase 2 clinical development in the first quarter of 2013.

Based on their unique mechanism of action, T-type calcium channel blockers such as Z944 have the potential to provide relief of pain and other symptoms in patients suffering from acute and chronic inflammatory pain, such as post-operative pain, fibromyalgia and inflammatory bowel syndrome, which are significant disease areas in which novel agents with improved tolerability, efficacy, and long-term safety profiles are needed,” commented Mark H.N. Corrigan, MD, President and CEO of Zalicus.

Zalicus is a leader in the discovery and development of Ion channel blockers, with unique expertise in N and T-type calcium channel and sodium channel blockers, and

an emerging pipeline of Ion channel blocker drug candidates, including Z160 our oral, N-type calcium channel blocker which is poised to enter Phase 2a clinical trials in neuropathic pain indications in the third quarter of 2012.

About Z944 and T-type Calcium Channel Blockers:

Z944, is a novel, oral, T-type calcium channel blocker that has demonstrated preclinical efficacy in multiple inflammatory pain models. A Phase 1 clinical trial evaluating the safety and tolerability of Z944 is ongoing. If Z944 successfully completes this Phase 1 clinical trial, Zalicus is planning to advance Z944 into Phase 2 clinical development.

The wide distribution of T-type calcium channels found in brain, heart, endocrine cells and other tissues provides the possibility of developing therapeutics for multiple indications, including treatment of pain.

Study provides clues to clinical trial cost savings

B iopharmaceutical companies could significantly cut the cost of clinical trials by reducing the number of non-

core procedures they perform.A new study has revealed ways to

streamline clinical trials and make them significantly less costly.

According to research conducted by scientists at Tufts University’s Centre for the Study of Drug Development (CSDD), the overall annual cost of clinical trials could be reduced by between $3 billion and $5 billion.

The researchers say that clinical data gathered from 25 per cent of the procedures administered to patients may be unnecessary, and that this leads to avoidable costs.

Their study, which was sponsored by Medidata Solutions, a global provider of cloud-based clinical development solutions, indicates that pharmaceutical companies could significantly reduce the amount they spend on clinical trials by cutting back on

procedures that are not core to the study protocol.

Ken Getz, senior research fellow and research assistant professor at CSDD, presented the findings at the annual meeting of the Drug Information Association.

He said: “This study is groundbreaking in that it links, for the first time, clinical trial economics to protocol complexity.

“The results have been eye-opening for participating companies and will no doubt serve as a jumping off point for pharmaceutical and biotechnology companies to examine ways to reduce the number of non-core procedures to improve clinical trial efficiency and substantially reduce study budgets.”

The study working group included Marla Curran, director of clinical statistics at GlaxoSmithKline, who has worked hard to increase efficiency across the company’s trials.

She said: “Even with this study’s conservative estimate of the procedures organizations could potentially eliminate, it’s clear that the industry can take a closer look at trial design to improve efficiencies while still meeting regulatory requirements.”

Source: cphi-online.com

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EYE ON CHINA

A n international team, led by Lanzhou University, comprising BGI, the world’s largest genomics organi-

zation, Institute of Kunming Zoology, Chinese Academy of Sciences as well as the other 12 institutes, has completed the genomic sequence and analyses of a female domestic yak, which provides important insights into understanding mammalian divergence and adaptation at high altitude. This study was recently published online in Nature Genetics. Scienceshot made a timely comment on yak genome themed “What gets yak high”.

As an iconic symbol of Tibet and of high altitude, the yak (Bos grunniens) is the most important domesticated species for Tibetans living at high altitude in China’s Qinghai Province, which could provide meat and other basic resources, such as milk, transportation, dried dung for fuel, and hides for tented accommodation. Yaks have many anatomical and physiological traits that enable them live at high altitude, including high metabolism, acute senses, impressive foraging ability, enlarged hearts and lungs, and a lack of blood vessel constriction in the

Yak genome provides new insights into high altitude adaptationlungs when faced with relatively low oxygen conditions.

In the study, researchers sequenced the genome of a female domestic yak using high-throughput sequencing technology. The genomic data yielded 2,657Mb draft yak genome assembly that had 65-fold coverage. They also conducted transcriptome sequencing on RNA samples derived from fresh heart, liver, brain, stomach, and lung tissues collected from the same yak. Based on the transcriptome data, researchers estimated that the yak genome contains 22,282 protein-coding genes and 2.2 million heterozygous SNPs.

In order to understand evolutionary adaptation of yak to the high-altitude, the team conducted the comparative genomic analyses between yak and cattle, a closely related animal that typically lives at much lower altitudes. Although the yak and cattle were estimated to have diverged around 4.9 million years ago, many of the yak and cattle genes have remained very similar, with the two animals sharing 45 percent protein

identity and 99.5 percent protein similarity. However, they identified distinct gene expansions related to sensory perception and energy metabolism-related in yak.

In addition, researchers also found an enrichment of protein domains related to the extracellular environment and hypoxic stress. Especially, they found the orthologous genes in yak related to hypoxia and nutrition metabolism had undergone positively selected and rapid evolution. For example, they found three genes that may play important roles in regulating body’s response to hypoxia, or oxygen deprivation, at high-altitudes, and five genes that were related with the optimization of the energy from the poor foods in the extreme plateau.

Researchers referred that the study on high-altitude adaptation may help to improve current understanding, treatment, and prevention of altitude sickness and other hypoxia-related diseases in humans. Moreover, the yak genome provided a valuable resource for accelerating the genetic improvement of milk and meat production of this important animal.

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EYE ON CHINA EYE ON CHINA

G entris and the Shanghai Institutes of Preventative Medicine will work together to accelerate healthcare

innovations in the US and China. Gentris Corporation and the Shanghai

Institutes of Preventative Medicine (SIPM) have announced a new collaboration aimed at advancing global personalised medicine.

The US-China collaboration will see Gentris, a global leader in applying genomic biomarkers to clinical studies, team up with the SIPM to create translational research and epidemiological projects.

It is hoped that the move will drive the development of new drugs and ultimately lead to improvements in patient care.

Gentris will identify sponsors for these personalised medicine projects - which will

Gentris and Shanghai Institutes of Preventative Medicine expand collaboration

focus on therapeutic areas such as oncology, infectious disease and chronic disease - in the US, with the SIPM doing likewise in China.

The two organisations have already worked together on tuberculosis and drug-induced liver injury, paving the way for an even broader translational research partnership between the two countries.

Dr Wu Fan, director of the Shanghai CDC and SIPM, said he was «excited» by the new collaboration.

"The goal of this partnership is to work with Gentris, a leader in pharmacogenomics and clinical sample management, to accelerate healthcare innovations in China and the USA that will improve public health globally,” he revealed.

Dr Tong Zhou, senior director of China initiatives at Gentris, added that he hopes the partnership “will advance the development of novel biomarkers that better predict the safety and efficacy of drugs”.

Source: cphi-online.com

C hinese researchers have identified a key gene in rice that could enhance both quality and productivity of rice

at the same time, as they reported in the journal Nature Genetics.

While studying the Basmati rice from Pakistan that is world famous for its high quality, Fu Xiangdong at Chinese Academy of Sciences and his colleagues found a gene named GW8 could influence the quality of rice.

Chinese researchers identify rice gene enhancing quality, productivity

The gene could improve the shape and color of rice grain, enhancing its quality of appearance. On the other hand, it could also change the arrangement of starch inside the grain, enhancing its quality for eating.

Further study shows that the GW8 gene also exists in some types of high yield rice grown in China. However, it’s a different variant of that gene, whose major effect is not on quality, but on the grain weight, thus enhancing the productivity of rice.

The team then identified a third variant of the gene. “We found another variant of GW8, which could combine the advantages of those two variants that respectively influences quality and productivity,” Fu told Xinhua in a telephone interview.

“Therefore the new variant could enhance the quality and productivity of rice at the same time.”

The superiority of the new variant of GW8 gene was supported by field experiments. If it is introduced into the Basmati rice, it could increase its productivity by 14 percent, while the quality remains the same.

And if it is introduced into the high yield rice in China, it could significantly enhance the quality of rice grains, while its productivity remains the same.

Fu said that this discovery could lead to new varieties of rice that would have outstanding performance in both quality and productivity.

Source: Xinhua

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EYE ON CHINA

T o better serve the rapidly growing demand for clinical development services in Asia, Quintiles joined local

government officials in officially opening its clinical development Center of Excellence in Dalian, a major hub of business and industry in northeastern China.

Quintiles Executive Chairman, Dennis Gillings CBE and several members of Quintiles Asia Management Board participated in the ceremony, celebrating this latest expansion of Quintiles investment in China. With a highly qualified, multilingual workforce and geographic proximity to Japan and Korea, Dalian is an ideal site to serve regional and international biopharmaceutical companies seeking to develop and market medicines in the region.

The Dalian Center of Excellence (CoE) is Quintiles’ fourth hub office in Greater China;

Quintiles opens new Center of Excellence in Dalian to support innovative drug development

its opening significantly enhances Quintiles ability to provide biopharma companies – particularly Japanese and Korean companies – with clinical development services, including data management, biostatistics, medical writing, and pharmacovigilance. The CoE will also serve as Quintiles’ hub to monitor clinical study sites in northeastern China and provide back-office support for Quintiles regional and global operation.

“From this Center of Excellence we can provide both clinical and non-clinical services in multiple languages including English, Japanese, and Korean to meet our customers’ drug development needs in a cost-effective fashion,” said Ling Zhen, General Manager and Head of Quintiles, Greater China. “Our multilingual abilities and cultural understanding of neighboring countries allows us to ‘think local and be

local’ – which is vital to helping our North Asian and global customers expand in the region.”

Qingwei Luan, Director of Dalian Hi-Tech Zone, said: “It is excellent news for Dalian to have the world’s largest biopharmaceutical services company open its clinical Center of Excellence in our city. Their decision to invest in Dalian is further proof of our city’s growth as a prime strategic location for international pharmaceutical companies in China.”

Located in Ascendas Park within the Dalian Hi-Tech Zone, the Dalian CoE is well-positioned to become one of Quintiles largest hubs in greater China to provide full-service offering to biopharmaceutical companies home and abroad to meet their drug development needs in the region.

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EYE ON CHINA EYE ON CHINA

B GI, the world’s largest genomics organization, announced that a group of scientists and researchers

successfully demonstrated genomic data transfer at a sustained rate of almost 10 Gigabits per second (Gbps) over a new link connecting US and China research and education networks. This data rate is equivalent to moving more than 100 million megabytes — over 5,400 full Blu-ray discs — in a single day.

The data transfer demonstration was part of a event in Beijing celebrating a new 10 Gigabit US – China network connection supported by Internet2, the China Education and Research Network (CERNET), the National Science Foundation (NSF), and Indiana University. Three centers and their representatives participated in the demonstration – BGI, Dr. Xing Xu, Director of Cloud Computing Product; University of California, Davis, Dr. Dawei Lin, Director of Bioinformatics Core of Genome Center; and National Center for Biotechnology

BGI demonstrated genomic data transfer at nearly 10 gigabits per second between US and China

Information (NCBI), Dr. Don Preuss, Head of Systems Group. Aspera Inc., the creator of the technology that moves the world’s data at maximum speed, provided software to support the data transfers.

BGI performed the live demos of ultra high-speed data exchanges between the three world-class genomics institutions. For example, BGI transferred 24 Gigabytes of genomic data from Beijing to UC Davis in less than 30 seconds. A file of the same size sent over the public Internet a few days earlier took more than 26 hours.

“The 10 Gigabit network connection is even faster than transferring data to most local hard drives,” said Dr. Lin. “The use of a 10 Gigabit network connection will be groundbreaking, very much like email replacing hand delivered mail for communication. It will enable scientists in the genomics-related fields to communicate and transfer data more rapidly and conveniently, and bring the best minds together to better explore the mysteries of life science.”

Dr. Xu said, “This was the first time that large genomic data were transferred between China and the US over a 10 Gigabit network. BGI is excited to demonstrate this achievement and looks forward to the potential opportunity to incorporate this breakthrough into our service capabilities to facilitate more rapid and efficient exchange of big genomic data globally.” Genomics has revolutionized the life sciences. While the cost of DNA sequencing is steadily decreasing, the amount of data generated with next-generation sequencing (NGS) technologies is growing at an unprecedented pace. In the age of “Big Genomics Data”, how to conveniently share the tremendous volume of data has become a significant research bottleneck. The 10 Gigabit Internet connection may provide a significant new tool for tackling “big data” and increasing scientific collaboration, education and cultural exchange between the two countries.

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EYE ON CHINA

I n a ceremony underscoring the growing importance of China to the global biopharmaceutical industry, Quintiles

executives and local dignitaries announced agreements to establish a Quintiles regional headquarters for China in Shanghai and to significantly expand lab testing capabilities in China.

Chenggang Zhu, Vice Mayor of the Shanghai Xuhui District People’s Government and executives from the Shanghai Clinical Research Centre (SCRC), Quintiles’ strategic partner in the China-based lab initiative, joined Quintiles’ executives at the ceremony.

“With its burgeoning economy and growing healthcare needs for its 1.3 billion citizens, China exemplifies the opportunities and challenges of the New Health,” said Quintiles Executive Chairman Dennis Gillings, CBE. “By broadening our investment and infrastructure here, Quintiles is ready to

Quintiles deepens investment in China - New Quintiles China Headquarters and local lab testing solution announced

partner with our biopharma customers as they look to realize China’s potential.”

Under a joint venture agreement, Quintiles will engage SCRC to provide lab testing services to local customers.

To provide the infrastructure essential for its growth strategy in China, Quintiles is investing US$14 million to establish a new 4,000-square-meter (43,000 square feet) headquarters in Shanghai to serve China and nearby Asian countries. The office in Feng Lin Science Park is designed to achieve LEED Gold accreditation; it is expected to accommodate more than 450 employees in the next five years.

“These investments and agreements demonstrate our commitment to this District and to China,” said Ling Zhen, General Manager for Quintiles’ operations in China. “Quintiles recognizes the unique needs of our customers in China. By collaborating

with SCRC in labs we can help local and international biopharma companies develop new and better medicines to serve China’s enormous unmet medical needs.”

Rongxing Gan, President of SCRC, said: “SCRC’s Central Laboratory’s experienced staff and modern technology will be further enhanced through Quintiles’ investments. We are delighted to work closely with Quintiles to further biopharma innovation and improve human health.”

The Quintiles-SCRC collaboration follows last year’s launch of Kun Tuo, Quintiles’ local contract research organization, built to help local and global biopharma companies achieve successful registration of medicines in China. Quintiles commenced operations in China in 1997, and has existing offices in Beijing, Dalian, Hong Kong and Shanghai, with employees and capabilities to serve all major population centers and study sites across China.

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A n international study, conducted by Bellvitge Biomedical Research Institute ( IDIBELL) , BGI, and

other collaborators, demonstrates that the DNA methylomes between newborns and centenarians are different, shedding important new light on how epigenetic marks degrade during aging. The latest study was published online in the National Academy of Sciences (PNAS).

The biology, physiology and medicine related with longevity and aging have been the research focus for decades. Scientists have discovered that genetic factors only contribute about 10 percent to longevity, while environmental factors contribute about 90 percent. Moreover, many identical twins studies have shown that environmentally induced differences are usually acquired via the epigenome.

Knowing that epigenetic modifications, especially DNA methylomes, are involved in numerous biological processes such as in human aging and diseases, researchers in this study performed whole-genome

B eike Becomes China’s First and Only AABB Accredited Stem Cell Bank and Sets High Industry Benchmarks for

Stem Cell Application in China Beike Biotechnology Co., Ltd (“Beike”)

announced that it has been awarded AABB accreditation for cord blood and cord tissue banking. This accreditation has been granted following an intensive on-site assessment by AABB assessors and establishes that the level of medical, technical and administrative performance within the facility is in accordance with the AABB standards or exceeds those set by AABB. With this achievement, Beike becomes China’s first and only AABB-accredited stem cell bank for both cord blood and cord tissue banking.

Ying Song, MD, PhD, Medical Director of Beike, stated, “It is a proud moment for us that Beike is the first and the only stem cell bank in China to possess AABB accreditation for both cord blood and cord tissue and this

Beike earns AABB Accreditation for cord blood and cord tissue banking

reflects our commitment to quality. It is also noteworthy to mention that Beike is among the first stem cell banks in the world to receive AABB accreditation for cord tissue banking which positions Beike as a leader in stem cell preservation.”

Beike began the comprehensive AABB accreditation process in March 2010 and completed the on-site assessment in September 2011. The accreditation assessment included stem cell processing, records, document control, inspection and testing, technician training, sample identification, traceability and validations. During this audit, it was determined that Beike’s medical, technical and administrative performance met the standards set by the AABB. Beike was issued its AABB certificate in January 2012.

Dr. Shengqin Ye, President of Beike, commented, “We are extremely pleased to have been granted this accreditation. With this, Beike has once again demonstrated

a commitment to advanced learning, continuous improvement and innovation to sustain the highest possible level of quality and safety.”

To meet AABB standards, Beike adopted new technology for stem cell processing (AXP® AutoXpress system), storage (BioArchive® Systems), and testing (Beckman hematology analyzer LH750 and Tecan Freedom EVOlyzer). Additionally, the company optimized its information technology platform and software systems, adding an advanced bar code management system, real-time monitoring capabilities, and an advanced enterprise resource planning (ERP) system to its call center.

Source: PRNewswire-Asia

bisulfite sequencing (WGBS) and compared the epigenetic information underlying the newborns, middle-aged persons and centenarians.

Through the analysis, they found that approximately 80% of all possible locations within the newborn’s DNA were methylated, but only 73% of the locations in the centenarian’s DNA were methylated. In all, methylated regions in the centenarian’s DNA were half a million fewer than that in the infant’s DNA. The regions include promoters, exon, intron, and intergenic elements, suggesting a regulated gene expression pattern in the centenarian.

The researchers extended their analysis to include DNA from larger groups of newborns and nonagenarians, and found a similar reduction in methylation of the nonagenarian DNA. Furthermore, analysis on DNA from middle-aged individuals revealed an intermediate level of methylation that fell between the two age extremes. All the results support a model of human aging

along with small changes in the epigenome, such as the varying DNA methylation, can accumulate over time and lead to broader changes in gene expression and cell function.

Dr. Ning Li, Director of BGI Europe, said, “The accumulative regulation of DNA methylomes may serve as one of the key marks to track human’s aging process. Our study further identified that epigenetic modifications played a crucial role in the aging mechanism. We look forward to achieving more breakthroughs in epigenomics research.”

Dr. Manel Esteller, PI of this project and Director of Cancer Epigenetics and Biology Program (PEBC), IDIBELL, said, “The research represents one of the few DNA methylation studies developed at a single-base resolution and the first one that analyzes the complete DNA methylome of newborns and centenarians. It provides important clues for the understanding of longevity, aging and their associated diseases, such as cancer.”

Epigenomic differences between newborns and centenarians provide insight to the understanding of aging

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FEATURE

Growing Cord Blood Cells for Cancer Patients

Ian McNieceThe University of Texas, MD Anderson Cancer Center, USA

Figure 1: Cord Blood mononuclear cells growing on MSCs.

T he use of umbilical cord blood (UCB) as a hematopoietic stem cell (HSC) source has been increasing in recent years and has

become an important source of HSC support following myeloablative and non-myeloablative therapies.1,2 Unfortunately, it is not without restrictions. The major limiting factor to UCB application is the low cell dose available for transplantation. It is well documented that the total nucleated cell dose (TNC) transplanted per kilogram (kg) of body weight of the recipient correlates with the outcome. Patients with a total body weight of at least 45kg who receive only a single unit of UCB have been shown to have a significant delay in time to neutrophil and platelet engraftment, as well as higher rates of engraftment failure.3 For this reason, UCB transplantation remains significantly more successful in children.4 However, even in small children who have received adequate cell doses, a delay is evident in engraftment of all cell lineages when compared to traditional stem cell sources5 as well as some delay with immune reconstitution.6

An obvious solution to this problem would be to grow more cells to overcome the delayed engraftment and immune reconstitution. This in fact has been the goal of many studies over the past 20 or more years. Ex vivo expansion is conducted on whole UCB units as well as selected portions; these expanded products can then be infused concurrently with an unmanipulated UCB, or sometime after infusion of the unmanipulated unit. Currently, clinical protocols aimed at proving the beneficial nature of this strategy are being conducted at a number of clinical centers.7-10

Many approaches have been explored for ex vivo expansion of UCB products

from liquid culture in bags to bioreactors. A number of groups have demonstrated that selection of CD34+ cells or CD133+ cells was necessary for optimal expansion. In 1997 we reported that culture of UCB mono nuclear cells (MNC) in a human growth factor (HGF) cocktail of stem cell factor (SCF) plus granulocyte colony stimulating factor (G-CSF) and thrombopoietin (TPO) resulted in only a 1.4 fold expansion of total cells, 0.8 fold in mature progenitor cells (GM-CFC) and 0.3 fold in erythroid progenitors (BFU-E) 11. In contrast, culture of CD34+ selected UCB cells resulted in 113 fold expansions of total cells, 73 fold expansion of GM-CFC and 49 fold expansion of BFU-E. Based upon these results we initiated expansion cultures in clinical trials with CD34-selected UCB cells.

Clinical Experience:Processing of clinical products in clinical studies has led us to two conclusions:

a) Although we can significantly expand the total nucleated cells (TNC) and committed progenitor cells from CD34+ cells, because of the significant CD34+ cell losses following the positive selection procedure, we rarely reached pre-selection TNC numbers.

b) The performance of clinical trials using UCB grafts in an unrelated setting requires the use of frozen UCB products. Selection of frozen UCB products results in significant losses of CD34+ cells (50% or greater loss of CD34+ cells) and often results in low purities12. With a 50% recovery of CD34+ cells after selection we now require

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FEATURE

Figure 2: Cord blood cells expanded ex vivo for 14 days.

at least a 400 fold cell expansion to obtain the equivalent TNC we started with. Again, from our experience with clinical studies, the purity of the CD34-selected product also impacted significantly the level of expansion achieved. The median-fold expansion obtained with products with purity greater than 50% CD34+ was 139-fold, while the median-fold expansion obtained with products with starting purities less than 50% CD34+ was only 32-fold13. Therefore the use of CD34-selected products rarely results in increased cell doses of ex vivo expanded cells compared to the starting unmanipulated product. Based upon these data we have evaluated methods for expanding UCB products without an initial CD34 or CD133 selection.

Recently two groups have reported on different culture approaches for ex vivo expansion that have resulted in exciting data in clinical trials demonstrating enhanced engraftment with ex vivo expanded cells.

Ex Vivo Expansion of Cord Blood Cells on Mesenchymal Stem Cells (MSCs) Based upon the ability of MSC to support hematopoietic cells, we have developed a co culture system which is capable of expanding UCB MNC by culturing the cells on confluent MSC layers13. The literature contains many reports of the ability of MSCs to support the growth of hematopoietic cells. It has been demonstrated that MSCs produce a number of HGFs and adhesion molecules that may stimulate growth of hematopoietic cells. Our data reproducibly demonstrated a 10 to 20 fold expansion of TNC with 18 fold expansion of GM-CFC and 16 to 37 fold expansions of CD34+ cells.

At MD Anderson Cancer Center, a clinical trial is underway combining an

unmanipulated UCB unit with an expanded UCB unit on a layer of MSCs. Myeloablative therapy for this protocol is ATG plus fludarabine, melphalan and thiotepa, and non-myeloablative therapy is ATG (antithymocyte globulin) plus fludarabine, cyclophosphamide and 200cGy TBI. On day 0, the unmanipulated UCB unit is infused, followed by the expanded UCB cells (from both the bags and the co-culture flasks). A median 12-fold expansion was seen in both the TNC and the CD34+ subsets. For the six recipients of myeloablative therapy, the median time to neutrophil engraftment has been 14.5 days (range 12-23) and platelet engraftment 30 days (range 25-51). Two of six patients developed Grade II Acute GvHD (graft versus host disease) which was resolved with steroids. One patient died of pneumonia in remission at day 150. Five of the six patients are alive and in complete remission at a median follow up of one year with accrual continuing14.

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References1. Stanevsky A, Goldstein G, Nagler A: Umbilical cord blood transplantation: pros, cons and beyond. Blood Rev 23:199-204, 2009

2. Goldstein G, Toren A, Nagler A: Transplantation and other uses of human umbilical cord blood and stem cells. Curr Pharm Des 13:1363- 73, 2007

3. Gluckman E, Rocha V, Arcese W, et al: Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 32:397-407, 2004

4. Gluckman E, Rocha V, Chevret S: Results of unrelated umbilical cord blood hematopoietic stem cell transplantation. Rev Clin Exp Hematol 5:87-99, 2001

5. Kurtzberg J, Prasad VK, Carter SL, et al: Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood 112:4318-27, 2008

6. Szabolcs P, Niedzwiecki D: Immune reconstitution after unrelated cord blood transplantation. Cytotherapy 9:111-22, 2007

7. Pecora AL, Stiff P, Jennis A, et al: Prompt and durable engraftment in two older adult patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated unrelated umbilical cord blood. Bone Marrow Transplant 25:797-9, 2000

8. Jaroscak J, Goltry K, Smith A, et al: Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. Blood 101:5061-7, 2003

9. Pecora AL, Stiff P, LeMaistre CF, et al: A phase II trial evaluating the safety and effectiveness of the AastromReplicell system for augmentation of low-dose blood stem cell transplantation. Bone Marrow Transplant 28:295-303, 2001

10. de Lima M, McMannis J, Gee A, et al: Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant 41:771-8, 2008

11. Briddell R, Kern BP, Zilm KL, Stoney GB, McNiece I: Purification of CD34+ cells is essential for optimal ex vivo expansion of umbilical cord blood cells. J. Hematotherapy 6:145-150, 1997

12. McNiece I, Briddell R, Stoney G, et al: Large scale isolation of CD34+ cells using the Amgen cell selection device results in high levels of purity and recovery. J. Hematotherapy 6(1):5-11, 1997

Notch Ligand Expansion of CB CD34+ Cells In a variation of the liquid culture technique, Delaney et al15 recently utilized an immobilized, engineered form of the Notch ligand Delta1 with recombinant cytokines (SCF, FL, IL-6, TPO and IL-3) to stimulate ex vivo UCB expansion. Ten patients with high-risk acute leukemias in morphologic remission, with a median age of 27.5 years and median weight of 61.5 kg, received myeloablative preparative regimen followed by infusion of one unmanipulated and one ex vivo expanded cord blood graft. All units were matched to the recipient at a minimum of 4/6 six loci and at least 3/6 matched to each other, with a minimum TNC dose in the unmanipulated graft of 2.5 × 107 TNCs/Kg. There was a 164-fold average expansion of CD34+ cells and 562-fold expansion of TNC. CD34+ cell dose derived from the expanded UCB graft averaged 6

× 106 CD34+ cells per kg (range 0.93 × 106 to 13 × 106) versus 0.24 × 106 CD34+ cells per kg (range 0.06 × 106 to 0.54 × 106) (P = 0.0004) from the unmanipulated UCB graft. There was no significant difference, however, in the average number of TNCs per kilogram. The time to ANC ≥ 500 cells/μl was shortened significantly (P = 0.002), with a median time of 16 days as opposed to a median time of 26 days (range 16–48 ; P = 0.002) in a concurrent cohort of 20 patients undergoing double UCB transplantation with identical conditioning and post-transplant immunosuppressive regimen.

Longer-term in vivo persistence of the expanded cell graft occurred in two subjects. In one subject, analysis at day 240 after transplant revealed that a portion (10–15%) of the donor CD14+, CD56+ and CD19+ cells were derived from the expanded graft but were no longer present by 1 year, at which point the donor engraftment was 100% from the unmanipulated cord blood graft. In the second subject, at day 180 after transplant, the contribution to engraftment from the

expanded cell population in CD33+, CD14+, CD56+ and CD19+ cells ranged from 25% to 66% of total donor engraftment.

SummaryUltimately, the goal of ex vivo expansion is the production of an optimal number of hematopoietic stem cells for graft transplantation as well as an appropriate number of specific progenitor cells for the purpose of rapid recovery from pancytopenia. A decrease in morbidity and mortality can be achieved if these goals can be met efficiently. The successful expansion with improved time to engraftment in the studies described above offer promise for studies to define the optimal cell population. The results of Delaney and colleagues demonstrate the potential of generating increased CD34+ cells, while the coculture studies on MSCs demonstrate delivery of increased number of TNCs. Future work should look at comparisons of the subsets of cells with each approach to better understand the need and contribution of these subsets to engraftment.

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Ian McNiece obtained his PhD from Melbourne University in 1986 and his thesis work was undertaken at the Peter MacCallum Cancer Institute under the direction of Drs Kriegler and Bradley. He did a post doctoral fellowship with Dr Peter Quesenberry in Charlottesville, Virginia and then worked at Amgen in California for 9 years studying hematopoietic growth factors. Dr McNiece returned to academia and worked at the University of Colorado in Denver as Director of Research in the Bone Marrow Transplant Program. He then moved to Johns Hopkins University as Professor of Oncology and Director of the Graft Engineering Laboratory. In 2004 he was appointed new director of the division of Biomedical Sciences of Johns Hopkins in Singapore. In 2007 he moved to the University of Miami where he was a Professor of Medicine and Director of the Experimental and Clinical Cell Based Therapies Program in the Stem Cell Institute. His work has focused on translational approaches using hematopoietic stem cells and the generation of cellular products for therapeutic approaches. In July of 2012 he moved to MD Anderson in Houston, Texas where he is the Director of the Cellular Therapy Laboratories where he oversees the clinical production of cellular products for clinical trials and standard of care procedures. His research laboratory is focused on developing culture conditions for optimal generation of cellular products for cardiac and hematopoietic therapies.

About the Author

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13. McNiece I, Harrington J, Turney J, et al: Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells. Cytotherapy 6:311-7, 2004

14. de Lima M, McNiece I, McMannis J, Hosing C, et al. Double Cord Blood Transplantation (CBT) With Ex-Vivo Expansion (EXP) of One Unit Utilizing A Mesenchymal Stromal Cell (MSC) Platform. Biol.Blood Marrow Transplant. 2009;15, 47-48.

15. Delaney C, Heimfeld S, Brashem-Stein C, et al: Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 16:232-6, 2010

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L eukemia patients and patients with other hematological diseases require transplantation of hematopoietic

stem cells available in bone marrow or mobilized peripheral blood. As with all transplantations, patient and donor have to be matched carefully on human leukocyte antigen (HLA) residues. Since the first successful transplantation of umbilical cord blood (UCB) into a young Fanconi Anemia patient in the eighties, cord blood has been increasingly used as a therapy for hematologic patients lacking a suitable HLA- matched donor. Since then, cord blood is collected at birth in several centers around the world and cryopreserved for later use in

Umbilical Cord Blood Transplantation in Adults The Debate between One vs. Two Units

Mary J. LaughlinUniversity of Virginia, USA

transplantation. For reasons not yet fully understood, cord blood transplantation results in less severe graft versus host disease (GvHD) complications post-transplant despite HLA mismatching, thus expanding the potential recipient pool significantly. However, to date, large scale application has been compromised by limiting cell doses single unit cord blood transplants causing problems, particularly in larger children and adults. While in the bone marrow transplant setting the donor can be solicited to donate again if engraftment is compromised, in the case of cord blood transplantation this is not possible, as collection is a one-time event.

The UCB total nucleated cell (TNC)

threshold cell dose for adult patients has been delineated to be a minimum of 2.5x107/kg recipient weight, resulting in favorable outcomes similar to that observed in patients receiving standard bone marrow or mobilized peripheral blood stem cell grafts from adult donors.1, 2 For larger adults however, such cell doses are difficult to attain with cells contained within one single cord blood collection (unit).3

More recently, two-unit UCB graft infusions has been explored in an attempt to overcome these graft cell dose limitations for adult patients in myeloablative and non-myeloablative setting.4 Important challenges to the analyses of clinical trials published

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to date include a variance in patient selection, a lack of uniformity in patient characteristics in those receiving one vs. two-units with a large proportion of single unit recipients being pediatric patients, as well as changes over time in conditioning and GvHD prophylaxis, including anti-thymocyte globulin (ATG) administration. Two large single institution series (published to date) report retrospective experience with patients transplanted with one or two UCB units after non-myeloablative conditioning.5,6 However, changes in the preparatory regimens used, patient selection differences including marked age variation, and modifications in supportive care including graft vs. host disease (GvHD) prophylaxis and ATG administration during the course of these studies, have rendered interpretation of potential benefit of two unit transplantation difficult. Importantly, however, two additional large retrospective series showed lower relapse rates particularly in early stage patients who received two UCB units, suggesting a benefit in transplanting two units.7

Interestingly, after a transient chimerism where cells of both cord blood units can be observed, one cord blood unit emerges quickly as dominant, from which long-term hematopoiesis is then derived. Potential UCB immunologic and stem cell homing mechanisms underlying the engraftment of the dominant unit are still unclear.

A recent prospective phase I/II study compared the safety and efficacy of one vs. two UCB units infused into adult patients. Importantly, the patients were treated uniformly with the same reduced intensity conditioning (RIC), GvHD prophylaxis, and supportive care regimen, to determine whether rates and kinetics of engraftment, acute GvHD incidence, relapse rates, and survival may differ after infusion of one unit compared to two units.8 This study also examines the influence, if any, of UCB graft infused TNC, CD34+ hematopoietic progenitors, natural killer (NK), and T-cell doses on procedure outcomes including: overall survival, allogeneic engraftment, and event free survival. The study design specified one UCB unit if the cryopreserved total nucleated cell dose was >2.5x107/kg recipient weight, otherwise 2-units matched

at minimum 4/6 HLA loci to the patient and 3/6 to each other were infused. Twenty-seven patients received 1 unit, 23 patients received two units. The median time to absolute neutrophil recovery was 24 days, with no significant difference between 1 unit recipients and 2 unit recipients. Three-year event free survival (EFS) was also similar in both patient groups.

Interestingly however, infusion of two units was associated with significantly lower relapse risk, with only 30% of the two unit patients relapsing, compared to 59% of the 1 unit patients relapsing. Infused cell doses (TNC, CD3+, CD34+, CD56+CD3neg) did not impact engraftment, overall survival, or EFS. Conclusions drawn from this study suggest that single unit UCB transplantation with a threshold cell dose >2.5x107/kg recipient weight after RIC is a viable option for adults, and that infusion of two units confers a lower relapse incidence to these patients.

This study was the first prospective investigation directly comparing a single UCB unit versus a two-unit approach in adult hematologic malignancy patients treated with uniform RIC and supportive care including acute GvHD prophylaxis. The patients enrolled were reflective of an adult hematology practice including the predominance of myeloid leukemia over lymphoid malignancy, and were comparable to other reports in terms of age and weight range. Of note, most patients included in previous reports on RIC outcomes with bone marrow and UCB grafts, had either none or had received prior autologous hematopoietic cell transplantation.4, 6,9,10 In this study however, patient population were extremely high-risk for disease and were heavily pre-treated, including over half of patients receiving prior autologous or allogeneic transplantation, implicating a possible higher risk of relapse- and non-relapse mortality. Despite this high risk, these data compare favorably to previous single institution trials and larger retrospective series, and recent data published by the National Marrow Donor Program summarizing transplant outcomes in adults treated with RIC and conventional adult-derived graft sources.4,6,11,12

A major concern for UCB transplant safety and efficacy for adult patients is

the limited TNC and CD34+ progenitor cell content in the graft, generally a log lower than adult-derived grafts.3 Several studies have shown neutrophil engraftment after UCB transplantation correlating with graft TNC dose, CD34+ cell dose, CD3+ cell dose and CD8+ cell dose. However, the influence of these graft cell populations is not seen consistently across all trials.

In the two-unit setting, infusion of two UCB units did significantly impact the relapse risk in high risk patients, with 1-unit recipients having a relapse risk significantly higher than two-unit recipients, suggesting a strong graft-vs. malignancy effect of two-unit UCB infusion as reported in prior retrospective studies.2, 7 Sixteen (59.3%) patients in the one-unit group in this study notably relapsed, compared to only 7 (30.4%) patients in the two-unit group (p=0.045). The benefit of stronger graft vs. lymphoma effect has also been reported by the Eurocord-Netcord and lymphoma working party of the European group for Blood and Marrow Transplantation in 104 adult patients treated with one- or two-unit UCB after RIC with lower risk of relapse observed in recipients of double-unit UCB (p=0.03).2

Consistently, one UCB unit predominates in transplant recipients receiving two or more UCB units usually by 4-6 weeks after transplant. Infusion of the non-engrafting unit may augment UCB engraftment via immune activation and/or inhibition of recipient-mediated immune rejection.14,15 Since RIC transplantation depends on “allogeneic effect” to eliminate malignancy, each UCB unit represents an intact immune system with potential donor-recipient and donor-donor interactions that may render additional benefits of two-unit infusion, including enhanced graft vs. malignancy effects. Despite of ongoing immune interactions between the two infused cord blood units and the patient, surprisingly there is no increase in acute or chronic GvHD frequency nor severity when infusing two cord blood units.

While single unit UCB transplantation at threshold nucleated cell dose exceeding 2.5x107/kg recipient weight remains a valid treatment option, it remains to be seen whether two unit transplants will become an option for adult patients where such a

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Mary J. Laughlin is a tenured Professor of Medicine at the University of Virginia and holds their Cancer Center Endowed Chair. Dr. Laughlin is a scientist of exceptional creativity who initiated her groundbreaking work in umbilical cord blood allogeneic stem cell transplantation while holding a post as Assistant Professor at Duke University initially in 1994 and has carried this work forward over the past 17 years. She has made important contributions to the field of hematology and stem cell transplantation, bringing forth this new stem cell source as an effective treatment modality for adult patients with life-threatening hematologic disorders, and providing new insights in neonatal hematopoietic stem cell and T lymphocyte biology.

About the Author

cell dose cannot be attained. The observed lower relapse risk after the infusion of two umbilical cord blood units, with similar survival outcomes seems promising, but current data available is insufficient, given the heterogeneity of patient populations

and the small number of patients studied in settings where patient characteristics and treatment were comparable. Further studies are needed in larger multi-institutional prospective trials: 1) to firmly establish the minimum safe threshold dose for single

unit UCB in adult patients treated with RIC, and 2) to identify key parameters for graft selection in the two UCB unit setting that may contribute to enhance graft vs. malignancy effects confirmed in this prospective single institution study.

References1. Rocha, V., M. Mohty, et al. (2009). “Reduced-intensity conditioning regimens before unrelated cord blood transplantation in adults with acute leukaemia and other haematological malignancies.” Curr Opin Oncol 21 Suppl 1: S31-34.

2. Rodrigues, C. A., G. Sanz, et al. (2009). “Analysis of risk factors for outcomes after unrelated cord blood transplantation in adults with lymphoid malignancies: a study by the Eurocord-Netcord and lymphoma working party of the European group for blood and marrow transplantation.” J Clin Oncol 27(2): 256-263.

3. Gluckman, E. and V. Rocha (2009). “Cord blood transplantation: state of the art.” Haematologica 94(4): 451-454.

4. Ballen, K. K., T. R. Spitzer, et al. (2007). “Double unrelated reduced-intensity umbilical cord blood transplantation in adults.” Biol Blood Marrow Transplant 13(1): 82-89.

5. Barker, J. N., D. J. Weisdorf, et al. (2005). “Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy.” Blood 105(3): 1343-1347.

6. Brunstein, C. G., J. N. Barker, et al. (2007). “Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease.” Blood 110(8): 3064-3070.

7. Verneris, M. R., C. G. Brunstein, et al. (2009). “Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units.” Blood 114(19): 4293-4299.

8. Kindwall-Keller T.L., Y.Hegerfeldt, et al. (2011).”Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies.” Bone Marrow Transplant. doi: 10.1038/bmt.2011.195.

9. Baron, F., R. Storb, et al. (2006). “Factors associated with outcomes in allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning after failed myeloablative hematopoietic cell transplantation.” J Clin Oncol 24(25): 4150-4157.

10. Mielcarek, M., B. E. Storer, et al. (2007). “Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors.” Biol Blood Marrow Transplant 13(12): 1499-1507.

11. Eapen, M., V. Rocha, et al. (2010). “Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis.” Lancet Oncol 11(7): 653-660.

12. Giralt, S., B. Logan, et al. (2007). “Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program.” Biol Blood Marrow Transplant 13(7): 844-852.

13. Laughlin, M. J., M. Eapen, et al. (2004). “Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia.” N Engl J Med 351(22): 2265-2275.

14. Fanning, L. R., Y. Hegerfeldt, et al. (2008). “Allogeneic transplantation of multiple umbilical cord blood units in adults: role of pretransplant-mixed lymphocyte reaction to predict host-vs-graft rejection.” Leukemia 22(9): 1786-1790.

15. Gutman, J. A., C. J. Turtle, et al. (2010). “Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit.” Blood 115(4): 757-765.

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O ver the last decades, umbilical cord blood (UCB) has emerged as a novel stem cell source. Already as

early as 1974 researchers had shown that UCB contains functional hematopoietic progenitor cells, that multi-lineage colony-forming units were present and that cryopreservation was possible. 1 This set the stage for cord blood as a source for clinical applications in hematological diseases. In 1989, the successful engraftment of UCB in a young patient with Fanconi’s Anemia demonstrated the feasibility of transplanting UCB instead of bone marrow. 2

Since then, hematopoietic stem cells (HSCs) from UCB are transplanted for hematologic reconstitution, and cord blood is now a widely accepted treatment for blood cancer, bone marrow failure and inherited hematologic deficiencies. As babies delivered represent the general population, a much larger pool of matched donors can be attained than for bone marrow, for which only a small fraction of the population is registered as donors. Umbilical cord is thus a good source of stem cells for ethnic minorities which are usually underrepresented in transplant registries

and have difficulties in finding a compatible donor. Additional advantages of UCB over bone marrow are that the collection is risk-free and painless to the donor and that UCB can be frozen and stored in banks and thus offers the advantages of an ‘off-the-shelf’ treatment.

Over the years it has emerged that beyond HSCs, cord blood and the tissue lining the cord itself contain other types of stem cells. Other than HSCs, cord blood contains endothelial progenitor cells (EPC), a low number of multipotent stromal cells (MSCs) and a rare population of unrestricted

Stem Cells in Umbilical Cord

Suzanne KadereitUniversity of Konstanz, Germany

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somatic stem cells (USSCs). The loose connective tissue surrounding the umbilical cord, called Wharton’s jelly cell (WJC), is rich in MSCs with properties similar to bone marrow MSCs. 3

As umbilical cord and blood are considered fetal tissue, it is not surprising that the stem cells therein are ‘younger’ than in the grown adult. It has been shown that HSC, MSCs and EPCs lose their potential with increasing age or with disease. For example, it was observed that the number of circulating endothelial precursor cells (EPC) and their functionality are reduced in smokers and patients with certain pathological conditions such as diabetes and coronary artery disease. 4 MSCs and HSCs also lose their regenerative capacity with increasing age. Thus, using autologous cells to transplant into older patients, that is, using their own stem cells mostly from the bone marrow, will likely not be very beneficial. Umbilical cord stem cells thus may provide better transplantation material than their adult counterpart.

In pre-clinical disease and developmental models, umbilical cord stem cells have been transplanted successfully and demonstrated regenerative potential. Accordingly, umbilical cord stem cells are under investigation as potential cell source for non-hematologic regeneration as for example cardio-vascular disease, spinal cord injury, Alzheimer’s and Parkinson’s disease, and as a potential source for immunotherapy and gene therapy. 3

Hematopoietic Stem Cells (HSCs)Umbilical cord blood is richer in HSCs than adult bone marrow. Thanks to its easy procurement UCB has become a mainstay for researchers investigating human HSCs. HSCs in cord blood are more primitive than their counterpart in bone marrow, with longer telomeres and a higher proliferation and differentiation potential. Expression of CD34 on human HSCs has been shown to correlate with human engraftment. Cord blood also contains very primitive HSC, lacking the expression of CD34 but capable of engrafting mice. Additional markers have been identified over the years. One such marker is the detoxifying enzyme

aldehyde dehydrogenase (ALDH). In mouse studies, all regenerative capacity seems to be contained within cells expressing ALDH. However, the relevance of CD34 negative and/or ALDH positive cells in the clinical setting remains to be evaluated. One marker that is already being used to purify HSCs for clinical transplantation is CD133. 5 Interestingly, CD133 is also expressed by the hemangioblast, the common precursor of the HSC and the EPC.

Endothelial Progenitor Cells (EPCs)Since their first successful use in therapeutic angiogenesis over 10 years ago, endothelial progenitor cells (EPCs) have been the focus of intensive investigation, as millions of cardiac patients could benefit from cellular therapies to improve blood flow. 6 EPCs reside in the bone marrow and home to sites of neovascularization where they differentiate into endothelial cells. Normally, circulating EPCs in our blood contribute to regenerative angiogenesis during ischemia, wound healing, and a variety of other pathological conditions in the adult. It was shown that vascular trauma and myocardial infarction induced a rapid mobilization of EPC into the peripheral blood.3 Unfortunately, the numbers and capacity of these cells decline with age and in diseases such as coronary artery disease and diabetes, there is a decreased capacity for repair in the aged and increased risk for cardiovascular events. This suggests that transplantation of younger EPCs could improve conditions caused by declining neo-angiogenesis.

EPC can also be isolated from umbilical vein and cord blood and have a similar phenotype as their adult counterpart. They are however more prolific than adult EPCs, generating more endothelial cells in culture, and forming capillaries faster. In pre-clinical animal models of therapeutic neovascularization for limb ischemia, cardiac regeneration and diabetic neuropathy, EPCs from cord blood performed better. 7 While vessels formed by EPCs derived from adult peripheral blood regressed within 3 weeks after transplantation, cord blood-derived EPCs formed stable blood vessels lasting for more than 4 months. 8

Multipotent Stromal Cells (MSCs) MSCs are cells residing in the bone marrow and adipose tissue that can generate bone, stroma, tendon, cartilage, muscle, fat tissue and neurons. Bone marrow-derived MSCs are starting to be used on a larger scale in the clinical setting where they are used to support ex vivo expansion of HSCs, engraftment of HSCs in leukemia patients, improvement of graft versus host disease and bone fractures. MSCs have one very interesting property: they can modulate the immune system and are not rejected by allogeneic immune cells, potentially being universal donor cells. In animal models they have also been shown the regenerate heart tissue. However, similar to other stem cells in the body they also age with their ‘host’. As human bone marrow is not an abundant source and collection is not risk-free to the donor, it was disappointing to realize that cord blood, similar to peripheral blood, did not seem to contain any MSCs. But improvements in culture techniques has enabled isolation of MSCs from cord blood that are very similar to bone marrow-derived MSCs. Similar to bone marrow or adipose tissue-derived MSCs, cord blood MSCs could be shown to generate bone, cartilage, tendon, muscle, fat tissue, stromal cells and neurons. Nevertheless, cord blood is a poor source of MSC, and much more MSC-like cells can be isolated from the surrounding connective tissue of the umbilical cord - Wharton’s jelly. These cells can be easily expanded in culture to large amounts. Again, as with other umbilical cord cells, they have a greater proliferation and expansion potential, compared to adult MSCs. WJCs have been used successfully to regenerate animal models of Parkinson’s disease, retinal degeneration and stroke. They have been used to derive tissue-engineered heart valves, pulmonary conduits, cartilage and bone constructs, making WJCs an exciting cell source for future tissue engineering work and regenerative medicine. 9

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References1. Nakahata, T. and M. Ogawa, Hemopoietic colony-forming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors. J Clin Invest, 1982. 70(6): p. 1324-8.

2. Gluckman, E., et al., Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med, 1989. 321(17): p. 1174-8.

3. Kadereit, S. and G. Udolph, eds. Umbilical cord blood: a future for regenerative medicine? 2010, World Scientific Press: Singapore.

4. Tepper, O.M., et al., Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures. Circulation, 2002. 106(22): p. 2781-2786.

5. Lang, P., et al., Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Haematol, 2004. 124(1): p. 72-9.

6. Zhang, L., R. Yang, and Z. Han, Transplantation of umbilical cord blood-derived endothelial progenitor cells: a promising method of therapeutic revascularisation. European Journal Of Haematology, 2006. 76(1): p. 1-8.

7. Finney, M.R., et al., Direct comparison of umbilical cord blood versus bone marrow-derived endothelial precursor cells in mediating neovascularization in response to vascular ischemia. Biol Blood Marrow Transplant, 2006. 12(5): p. 585-93.

8. Au, P., et al., Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood, 2008. 111(3): p. 1302-5.

9. Kadereit, S., Umbilical Cord Stem Cells, in Stem Cell Labeling for Delivery and Tracking Using Noninvasive Imaging, D. Kraitchman and J. Wu, Editors. 2012, CRC Press: Boca Raton, FL, USA. p. 87-101.

10. Riordan, N., et al., Cord blood in regenerative medicine: do we need immune suppression? Journal of Translational Medicine, 2007. 5(1): p. 8.

The Unrestricted Somatic Stem Cell (USSC) UCB also contains a pluripotent stem cell capable of generating tissue of endodermal, mesodermal and ectodermal origin. This cell was named unrestricted somatic stem cell, (USSC), and is a rare cell that can be isolated from roughly only every third cord blood collection. This cell has been shown to be able to generate blood cells and to engraft in animal models. The USSC can also generate neurons, glial cells, liver cells, cardiac cells, as well as the cell repertoire

generated by MSCs. It appears that the USSC may be a precursor cell of MSCs. USSCs share overlapping features with MSCs isolated from fetuses, can contribute to both injured and developing tissue, and support engraftment of HSCs. USSCs can be isolated and grown in culture to significant amounts and when transplanted into animal models these cells persist for months, making them very attractive cells for cellular therapies.

ConclusionsThe last years have shown that umbilical cord and its surrounding tissue are rich in human stem cells. The abundance of umbilical

cord and ease of procurement make it a very attractive source of human stem and progenitor cells for clinical applications, raising the hope that umbilical cord stem cells could one day be used on a large scale in regenerative medicine for cardiac disease, diabetes, neurodegenerative diseases, orthopaedic reconstruction, tissue and biomedical engineering. 10

As umbilical cord reflects the population surrounding the maternity which collected the cord, it provides a large pool of matched donor cells for that population. This provides hope for all patients that are not represented in organ donor registries, and waiting on transplant lists to benefit from life-saving therapies.

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Cord Blood BankingTo Go Public or Stay Private

Vivek TanavdeBioinformatics Institute, Agency for Science Technology & Research (A*STAR), Singapore

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B anking cord blood is increasingly becoming popular in many countries in the world. Cord blood banks are set up

as public banks or private banks that provide these services for a fee. Parents are often faced with the dilemma of whether to choose a public bank or a private bank for storing their child’s cord blood. This issue has been hotly debated, often with proponents of both public & private banks opposing the other’s model. However both public and private banks can co-exist as it is impossible for governments to fund public cord blood banks to meet the growing demand. This is especially true in Asia which is home to a growing population and demand for cord blood banking. This article explores the commercial aspects of cord blood banking including the necessity for private banks and hurdles faced by them.

Cord blood is a rich source of stem cells that is often discarded. Since cord blood can only be collected at the time of delivery, it has to be ‘banked’ or cryopreserved for future use. Cord blood banks are either funded by public money, where the cord blood is stored at no cost to the donor or are run by private companies where the donor pays for the processing and storage of cord blood units. Parents deciding to store cord blood must choose between public or private cord blood banks. Since public banks are funded by public money, they are limited by the number of units they can successfully store. Public banks accept cord blood units as donations to be used for transplantation of patients without the possibility for the donors to choose their recipient candidate. Once the blood is donated, it loses all identifying

information after a short period of initial testing, so that families will not be able to retrieve their own blood units later. Since many parents may want to reserve their child’s cord blood for his/her own use or for their siblings, they may opt to use a private cord blood bank and pay for banking their baby’s cord blood. This need has given rise to a number of private cord blood banks in different parts of the world and many of them are getting incorporated and publicly listed on the various stock exchange.

Is Private Banking Necessary?The larger obstacle facing banks funded by public money are the costs required to run and maintain them. This has prevented more than a handful from opening worldwide. Because public banks do not charge storage fees, many medical centers lack the funds required to establish and maintain banking operations. Due to donation patterns, different racial groups have different likelihood of finding a match through a public cord blood bank. For example in the New York Blood Center, the largest bank in the US, Caucasians will find a match 70% of the time (5-6/6 HLA match) [1], while the probability of finding a match is considerably lower for ethnic minorities. This encourages people to store their child’s cord blood for his/her own use.

A number of pr ivate-for-prof i t companies have been established that encourage parents to bank their children’s cord blood for their own autologous use or by a family member, should the need arise. Parents have been encouraged to bank their children’s cord blood as a form of “biological insurance.”

Physicians, employees, and/or con-sultants of such companies may have potential conflicts of interest in recruiting patients because of their own financial

benefit. Annual disclosure of the financial interest and potential conflicts of interest must be made to institutional review boards

that are charged with the responsibility of mitigation of these disclosures and risks. Families may be vulnerable to the emotional

effects of marketing for cord blood banking at the time of birth of a child and may look to their physicians for advice. No accurate

estimates exist of the likelihood of children to need their own stored cord blood stem cells in the future. Available estimates range from 1 in 1,000 to more than 1 in 200,000 [2]. Moreover, currently, the strategy for children receiving their own cord blood stem cells for future autologous use is controversial [2]. There is also no evidence for the efficacy of autologous cord blood stem cell transplantation for the treatment of malignant neoplasms later in life [2]. On the contrary, there is evidence demonstrating the presence of DNA mutations in cord blood obtained from children who subsequently develop leukemia [3]. Thus, autologous cord blood transplantation might be contraindicated in the treatment of a child who develops leukemia. Many organizations like the American Academy of Pediatrics explicitly discourage private cord blood banking if there is no family history of genetic disorders or familial cancers [4].

Hurdles of Private BankingHigh costs for customers: The high cost coupled with lack of knowledge about the use of cord blood stem cells is the single largest deterrent to widespread adoption of cord blood banking. However many cord blood banks are developing innovative financing schemes to solve this problem.

Operational Issues: Private cord blood banks face some unique operational issues that are not faced by public banks. The biggest decision is when to bank a cord blood unit. Public banks have reasonably defined criteria for determining if a cord blood unit is bankable or not and units which do not meet these criteria are simply discarded or are used for research. However, for most private banks, this decision is usually taken by the client.

Legal and Ethical Issues: There are also some unique medical and legal issues facing private cord blood banks. Do the parents, the child or the cord blood bank own the

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FEATURE

Dr. Vivek Tanavde is currently a Principal Investigator at the Bioinformatics Institute, Agency for Science Technology and Research (A*STAR), Singapore. He obtained his Ph.D from the Cancer Research Institute, Mumbai (1999) in Applied Biology. From 1999 to 2002 he was a post doctoral fellow at the Sidney Kimmel Cancer Centre, Johns Hopkins University working on expansion of hematopoietic stem cells. He returned to India in 2002 and was heading the Hematopoietic Stem Cell Lab at Reliance Life Sciences, Mumbai. His laboratory also provided diagnostic services using flow cytometry, mainly in the areas of CD4/CD8 enumeration & single-platform CD34 enumeration. In 2006, he joined the Bioinformatics Institute, Singapore as a Research Scientist in the Genome & Gene Expression Data Analysis Division. Most of his work has focused on developing protocols for expansion and targeted differentiation of hematopoietic and mesenchymal stromal cells (MSC). His current research focuses on the use of bioinformatics and systems biology tools to understand mesenchymal stromal cell biology and differentiation. He is currently investigating the role of micro-RNAs (miRNAs) in regulating differentiation of MSC. He has 18 peer reviewed publications, 4 book chapters and 1 international patent to his credit in the area of stem cells.

About the Author

cord blood unit? What are the rights of the clients in case of total loss, or loss of quality of their cord blood unit due to poor storage, considering the life-saving value of cord blood stem cells, particularly with foreseeable expansion of cord blood use in non-hematological applications? These issues need to be addressed by the cord blood banks.

Long term storage: Since cord blood units cannot be duplicated and backed up, the storage facility should have multiple redundancies built into their systems to ensure uninterrupted functioning of the facility over the long run. The other problem that clients face is the fate of their cord blood units if the company goes out of business. Many banks now offer parents the

option to transfer their cord blood units to other banks in the event that the existing bank ceases operation.

However in spite of these issues, private cord blood banks are being established in many countries. Most parents who preserve their child’s cord blood see this as an investment in their child’s future. Although currently cord blood cells are therapeutically used only for blood disorders, there is potential for cord blood cells to be used for other disorders in the future. Autologous transplantation of cord blood cells may be used therapeutically in the future for diseases such as Parkinsons & osteoporosis. Since cord blood cells can only be collected at the time of birth, banking these cells at the time of delivery is the only way to

ensure that these cells will be available in the future. Since public banks cannot guarantee that the child’s cord blood will be preserved for autologous use, parents who can afford cord blood banking will demand for the opportunity to bank their child’s cord blood in a private bank. As the price of banking decreases with increasing numbers of private banks and ensuing competition, more parents will be able to afford banking cord blood. The lowering costs of banking cord blood will also reduce the financial burden of banking on the family.

Therefore, although private banking is still expensive, the expanding therapeutic uses of cord blood will make them more attractive in the future and private cord blood banks will likely continue to co-exist with public cord blood banks.

References1. Schoemans H, Theunissen K, Maertens J, Boogaerts M, Verfaillie C, Wagner J: Adult umbilical cord blood transplantation: a comprehensive review. Bone Marrow Transplant 2006, 38:83-93.

2. Johnson FL: Placental blood transplantation and autologous banking—caveat emptor. J Pediatr Hematol Oncol 1997, 19:183-186.

3. Rowley JD: Backtracking leukemia to birth. Nat Med 1998, 4:150-151.

4. AAP: Frequently Asked Questions about Cord Blood Banking. 2007.

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PEOPLEWATCH

APBN: How did you come up with the idea of OSDD?

Samir Brahmachari: I was involved in genomics and as director of the Council of Scientific and Industrial Research’s (CSIR) Institute of Genomics and Integrative Biology, I realized that we have to develop a systems biology approach to understand complex diseases. I saw that TB is the most devastating disease in India – a 1000 people die every day yet the genome sequence of the TB-causing microbe has been available for almost a decade, which means it should have been easy to target genetic vulnerabilities of the microbe. At the same time, I could also see the cost of human genome sequencing coming down, so I simply asked, if human genome sequencing and its analysis was done in public domain and made open source, why can’t we take drug discovery to open source? What are the hurdles that we face? I knew that Indian laboratories had done exceptionally well to do generic drug synthesis and Indian companies had been successful in taking those generics to market. That means we are very good at development – specifically low-cost development. CSIR has the tradition of drug development at affordable costs to make Indian generics the world leader. So what is missing? We did not invent new drugs. So the idea was very simple, OSDD is open source drug discovery. If I can make a drug discovery cheaper with high efficacy without side effects, using a systems biology approach, we should then be able to take it further to development at a low cost.

APBN: Why is open innovation the future of drug development?

Samir Brahmachari: The reason is that difficult problems need multiple expertise. It is very difficult to gather them together physically but it is easy to gather them on cyber-space. Look at the way Facebook users work and interact and it’s easy to see why open innovation is more successful. Another reason, is if we look at the way we develop an F1 car, we don’t build a car and then drive the car. Instead, we simulate the car on the computer and then make 5 prototypes which are then put into the wind tunnel and finally 2 cars are manufactured and one runs the race and wins it.

I believe the drug discovery of tomorrow will be heavily dominated by the in-silico experiments where one should be able to simulate everything and see where the drug is going, what are the pathways what are the other possibilities and based on that eventually molecules will be made whose failure rate will decrease by a factor 10 or 20. This will

Open SourceThe Future of Drug Discovery

I n the world of big pharma, it used to be the case that secrecy paid off big-time. Why risk revealing your drug-discovery pipeline when your competitors may just jump on the band-wagon and eat into your market-share? This model no longer holds water in an era of spiraling healthcare costs and the increasingly inter-disciplinary nature of medical science.

Secrecy and counter-productive, profiteering IP policies have now given way to a model that literally seeks openness in both name and function. Established in 2008 under the auspices of India’s Council of Scientific and Industrial Research (CSIR), the Open Source Drug Discovery (OSDD) network has gathered resources for developing drugs that pharmaceutical companies don’t find attractive enough. In an exclusive interview, OSDD’s founding father, Professor Samir K. Brahmachari tells APBN why it pays in more ways than one, to be open.

Interview by: V.K. Sanjeed Edited by: Sulastri Kamis

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reduce the cost from a billion dollars to a few million dollars. Furthermore, if the Indian generic industry has demonstrated that even a generic drug can make substantial profit, there should be no reason why companies will not participate in taking up new invented molecules which will become generic because it will be shared by others.

APBN: What are some unique features of India’s bio-research landscape that make OSDD a success?

Samir Brahmachari: India is still a resource limited country. Our resources might have increased, but it is still much less than anywhere in the world, particularly when compared to developed countries such as America, Japan and even China and European countries. But I think we have a very large student community that is very hungry to learn and which is really passionate. I think OSDD has been able to convert this activity from a professional enterprise into an emotional enterprise and young people are committed emotionally. And that, I think, is the strength of OSDD in India. Overall however, in India, we do not have too many experienced scientists who have actually discovered new molecules for drugs. This is something I hope to change with OSDD.

Another factor is India’s strong tradition of supporting anything that benefits the poorest of the poor. Profiteering is not the ultimate motto. You are more respected if you have been able to provide benefit to the bottom of the economic pyramid. It also helps that the government has invested heavily in a high GB bandwidth connectivity across the country that is available to people at zero cost. All these things make India an ideal place for OSDD to flourish.

In India, our science and scientists are very hierarchical. We respect our seniors, even if our senior is not making a right statement we will not argue. Instead, we will respect it and that’s the way our culture and family is. This is not good for science. Respect and seniority should not impede science. In cyberspace, something happens to us. We get out of our own cultural roots and try to become different. Things that we hesitate to tell our wives face to face, we have no difficulty communicating to them on social media. This is an interesting phenomenon that is advantageous for the development of Indian science which has been hampered for too long by a respect for hierarchy and seniority.

APBN: What are some of the challenges to the open source model of drug discovery?

Samir Brahmachari: OSDD is sharing drug discovery data and I believe we can do open source clinical trials, but I need to convince regulatory authorities that once the safety phase 1 is cleared, phase 2A where there is a limited number of patients, demonstrates safety. We also need to go into e-clinical trials where the data will go up and volunteer patients will join looking at the public domain data and then decide whether they want to participate or not. It is happening in various diseases, where there is no treatment even in the USA. Patient groups are taking an interest in any new molecules at the laboratory level. I think this would be a new challenge as it represents a fundamental shift in both patients and doctors mindsets at the clinical level.

APBN: There has been a lot of talk about the big pharma model of drug discovery falling apart. Why is this happening?

Samir Brahmachari: I have not worked in a big pharma so it will not be possible for me to reveal internal information but from what I understand, pharma companies are big on confidentiality clauses. It gives the company a big advantage over others but the weakness of the system is that it does not allow everybody’s brain power to come together. In contrast, look at the success of IT, whether it is Apple or Zuckerberg’s Facebook, all of this is possible because of youth – not some company. Pharma by virtue of its structure of organization, is not able to utilize the brightest. Young students never join pharma and anyone who joins pharma, joins as the technical support or as a middle-aged person after a certain amount of time in academia. I do not know of any 22, 24, 25 year-old fresh PhD rushing to pharma,

I believe OSDD is not a research project - it is a movement, an emotional enterprise, with clear, well-defined, worthy, real-world goals.

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whereas in IT it happens the other way. Somebody who could have been an assistant professor in Berkeley or Stanford is actually coming up with new innovations and spinning out MNCs. I think this is the problem with big pharma – it’s failed to attract young people with fresh ideas because its processes are obsolete.

APBN: Even if OSDD is open source and online, any user still requires a number of years of experience in medicinal chemistry and cell biology to understand and contribute to the field constructively. Doesn’t this platform still favour the more experienced researchers?

Samir Brahmachari: You would be quite surprised to know that on our OSDD platform I think 70% of people are below the age group of 35 and these young people are undergrads. And even those who are studying their bachelors of science and master of science, are participating in complete genome annotation, pathway analysis and we are picking up very unusual and bright kids. Since every contribution is recorded I can see on my computer who is contributing so I can always pick up a bright student sitting in a remote place and I can say hey, come and join this program as a PhD student or young faculty staff. So it is very easy to identify people who might have not done very well in their exams and university grades who might have difficulties in getting admission to organizations or getting into a fellowship, yet are fantastic at coming up with solutions to complex problems.

I just wrote a paper with 50 students from 26 institutions and I don’t know them. I only know 3-4 of the important ones and, yes they needed guidance. But they have the drive to do things and get back to you. I personally feel empowered that I can sit in a small building and make my world my laboratory and get a project in and review it and have India’s youngest best minds to tap on.

APBN: One of the principles governing the conduct of clinical trials under the CSIR/OSDD umbrella but with the Open Source concept is that private pharma will be stakeholders. Tell us why this is important.

Samir Brahmachari: Indian pharma companies have demonstrated that they can make molecules at low cost on an industrial scale and maintain quality and market it. The idea behind the principle is that we should be able to take more than one partner who would contribute to the clinical trials cause. The general idea is to take 20% cost from the company and 80% will be borne by OSDD and of the 20% maybe 4 companies will come in together so that brings it down to 5% each. There will be various teams doing the clinical trials. They will all get the manufacturing rights along the way.

APBN: After TB and malaria, what other diseases does OSDD intend to target?

Samir Brahmachari: We have already initiated for malaria and we have no problem and anybody can call it OSDD as long as the drugs produced become affordable and so we are working with others. We believe that leishmania should be the next one which is also a problem in India, next only to cholera. Beyond that, I think the most interesting and challenging will be to discover drugs for chronic long-term diseases which are always very expensive. Pharmacogenomics principles may be applied to identify the right drug for the right patient.

APBN: Besides OSDD, what other kinds of open source development models do you foresee for biomedical science?

Samir Brahmachari: We have prepared open source pharmacogenomics and some of my young colleagues have already started and we have taken the initiative with global effort again. If everybody shares pharmacogenomics markers, in a public domain, patients can actually get the benefits for a particular low cost drug for cancer it might have some side effects in x% of people, wouldn’t you like to know that you don’t belong to that percentage and thereby effectively you can reduce the public health costs significantly?

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APBN: When you speak of drug development expertise, what specific qualifications and skills are you looking for?

Samir Brahmachari: This is a question I asked myself before Sanger introduced DNA sequencing, as he was an expert on protein sequencing and that’s why he got the Nobel Prize. If we were to advertise we wanted somebody who has relevant to discover DNA sequencing knowledge then we might not have selected Sanger - Cambridge might not have selected Sanger. My point is that drug discovery is a new science and we are trying to use a systems biology approach. So it will need people with a medical background, medicinal chemistry background, techniques and systems level understanding background, mathematical and computing and simulation, chemical engineers and electrical engineers who know how to create the simulation, in short, all the faculties are needed. We also need to write protocols for new molecules in clinical trials for phase1 and phase 2 which is an expertise that we need to look at.

Perhaps most importantly, we need people who want to solve problems. With such a heterogeneous, inter-disciplinary team – fun in its own way – managing it can be an uphill battle. Leadership with strong goals of solving problems is lacking. What we are looking for is somebody who has at least 2-3 domains of expertise, somebody who is an IT person, who understands networking as well as hardware, software and biochemical pathways. It could even be someone who understands chemistry, computing and docking. Classically these are compartmentalized subjects and there’s a flow of molecules that goes through these compartments of knowledge. In OSDD we realized that we needed inter-disciplinary minded people and that’s what we are looking for. We are also looking for one person to be a brand ambassador for OSDD. This person will be a great communicator and write about OSDD.

I believe OSDD is not a research project - it is a movement, an emotional enterprise, with clear, well-defined, worthy, real-world goals.

APBN: What can Indian universities do to develop more inter-disciplinary minds?

Samir Brahmachari: We have realized that our education system is reasonably compartmentalized and not enormously multi-disciplinary but my CSIR laboratories are a chain of laboratories from biology to engineering to chemistry all put together, providing a unique opportunity to expose graduate students to get exposed to this type of multi-disciplinary type of environment. Very recently we have approval from parliament to set up an academy of scientific research which is called APSIR. It is like a mega university but it is a network environment because these laboratories already exist. The students will come and work in the same laboratories but the academy is an umbrella organisation which makes sure the posts are connected, standards maintained, comprehension is done and the students go to the programs and eventually participate and get a PhD. This is a step in the right direction to develop inter-disciplinary thinking and an innovative culture – both bywords of 21st century science.

Prof. Samir Kumar Brahmachari pioneered functional genomics initiative in India and led the Indian Genome Variation Consortium Project as the founder Director of CSIR-Institute of Genomics and Integrative Biology. His core expertise is in structural and computational biology. He has more than 12 patents, 23 copyrights and 150 research publications to his credit. Since, November 2007, he has assumed the office of Director General, Council of Scientific and Industrial Research (CSIR), which is the largest publically funded organization involved in scientific and industrial research with 37 constitutional laboratories across India. He has been the member of HUGO council (2004-2011), and is currently on advisory board of X-prize in Genomics. As a member of expert group on Human Rights and Biotechnology Commission of United Nations, he has addressed the issues of unethical exploitation of genetic resources of the third world and has championed the concept of right of patients in benefit sharing in the development of genomic medicine. He is the recipient of large number of National and International awards and an elected member of all four academies of science and engineering in India. He has been recently nominated as one of Fierce’s Top 10 Biotech Techies (www.fiercebiotechit.com) for his outstanding contribution to the field of genomics and Open Source Drug Discovery (OSDD). Science has hailed him as “Open-source guru” (2012) considering his exceptional contribution in conceptualizing and mentoring India’s first crowd – sourcing initiative – Open Source Drug Discovery.

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O cular toxoplasmosis is an infective condition of the eye caused by a parasite called Toxoplasma gondii.

Its main host are cats. Toxoplasma cysts are excreted in cat faeces, mature in the environment, and may be ingested by secondary hosts (humans, cattle, sheep, pigs, rodents and birds).Humans can be infected by the following routes:• ingesting/handling undercooked or raw meat (pork and lamb particularly)• ingesting/handling contaminated soil, water or food• direct contact with domestic cats• transmission from the mother to the child during pregnancy

Infection is usually congenital (tran-smission from the mother during pregnancy), but it can occur in any age group (acquired). Once the parasite is in the body, it will reach the eye via the blood stream and will establish itself in the retina (the light sensitive layer of the eye). It will form cysts which contain hundreds to thousands of organisms, and depending of the immune status of the host, the dormant cysts can remain encysted in host tissues, or the cysts breakdown and release the parasites in the retina, causing ocular diseases.

Ocular toxoplasmosis may present in the following ways:Congenital infectionA large atrophic scar, frequently in the macula – a result of congenital toxoplasmosis – is usually seen. Children who acquire the

Ocular Toxoplasmosis

Figure 1. Photograph of retina showed 3 retinochoroiditis scar due to ocular toxoplasmosis

Dr Alok AgrawalMS,Ph.D.

Dr. Jyotirmay BMS, FAMS, FIC Path

disease from their mother during pregnancy may be born with large scars in the “macula” and consequently with very poor vision. Since the infection destroys the retina and the retina cannot repair itself, visual loss is permanent.

Acquired infection• Patient with acquired infection may present the following symptoms:• Sudden onset of blurring of vision.• Black spots moving in front of the eyes.• In some cases, pain, redness and light sensitivity.

The vision of the patient with toxo-plasmosis is reduced for several reasons:• The lesions mostly involve the central part of the retina (macula) that is responsible for our central vision.• The inflammation may cause opacification of the vitreous (a jelly-like substance present inside the eyes, in front of retina).

After adequate treatment, the lesions become healed, however it will leave a scar. If the scar is located around central retina (macula) or optic disc, visual acuity will be decreased permanently.

Prevention1. Wash hands before handling food. 2. In case of cats, it is important to wash your hands, after handling the animal and especially after cleaning the litter box. Clean the litter box daily.3. Wear gloves and wash hands after handling soil and gardening.4. Avoid ingestion of poorly cooked or raw meat.5. Thoroughly wash all fruits and vegetables before eating.6. Drink bottled water in areas where you may not be certain of the origin of the water.

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Dr Alok Agrawal graduated from India in 2003. After his undergraduate degree, he went and did a long-term observership in different eye hospitals in the United States. He received his Postgraduate degree in Ophthalmology from India in 2008 and P.h.D in Ophthamology in 2011.

He did his long term fellowship training in Uveitis in 2008 at Sankara Nethralaya, India and later has acquired a wealth of experience in managing patients with a variety of complex ocular inflammatory diseases after doing another International Clinical Fellowship in Ocular Immunology & Inflammation Services from Singapore National Eye Center, Singapore in 2010.

Dr Alok’s uveitis research interests are mainly in Vogt-Koyanagi Harada Disease, Cytomegalovirus infection in the immune-competent. Dr Alok’s other passion is in uveitic cataract surgery. He is a member of various eye societies and has numerous publications in peered review journals. He is actively involved in research and has given talks in various conferences globally.

Dr J Biswas is an ophthalmologist who has specialized in uveitis and ophthalmic pathology. He has done MBBS from Medical College, Calcutta and post-graduate studies in ophthalmology from PGIMER, Chandigarh, and fellowship in vitreoretinal surgery from Sankara Nethralaya.

About the Authors

Treatment of Ocular ToxoplasmosisNot everyone who has ocular toxoplasmosis require treatment. A scar from congenital origin does not require treatment. In acquired infection, if the lesion is situated in the centre of the retina (macula) or near the optic nerve, permanent loss of central vision may occur and these patients may require aggressive treatments.

Antibiotics are importantThe standard treatment includes a com-bination of antibiotics like Clindamycin and Azithromycin. The treatment is usually given for four to six weeks during an active attack but maybe longer. The duration of treatment differs with the individual and depends on the severity of inflammation. Unfortunately, the current drugs available do not eliminate

the dormant form of Toxoplasma from patients against possible infection.

In addition to antibiotics, corticosteroid tablets are also necessary to reduce inflammation during an acute attack. However, it is essential never to use these tablets alone, but always together with antibiotic drugs. Typically, corticosteroids are added to treatment 1-3 days after commencing the anti-parasitic drugs.

Pregnant women and Ocular toxoplasmosisPregnant women who have ocular toxo-plasmosis are not normally treated unless they have dangerous or severe symptoms, because the medications might be of considerable risk to the fetus, especially in the early stages of pregnancy. However, the antibiotic Spiramycin is given to pregnant women with systemic toxoplasmosis to prevent infection to the fetus.

Figure 2. Photograph of retina showing ocular toxoplasmosis. Note that lesions can involve any part of the retina - centrally and peripherally.

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International Conference & Exhibition of the Modernization

of Chinese Medicine & Health Products (ICMCM)

Annual Pivotal Event for Global Chinese Medicine Industry16–18 August, Hong Kong Convention & Exhibition Centre

T he 11th edition of the International Conference & Exhibition of the Modernization of Chinese Medi-

cine & Health Products (ICMCM) will welcome more than 100 exhibitors from eight countries and regions. There is also group representation with pavilions from Guizhou, Jilin and Qinghai in the Chinese mainland.

Jointly organised by the Hong Kong Trade Development Council (HKTDC) and the Modernized Chinese Medicine International Association (MCMIA), the event will run 16-18 August, with the first two days open to trade visitors before public visitors will also be admitted on 18 August.

This event is a well-established platform that brings together those interested in the modern practice of this ancient tradition to meet exhibitors and to witness the latest developments as presented by practitioners and researchers.

ICMCM ConferenceHighlights of the event include the two-day ICMCM Conference to be held with the theme “Chinese Herbal Medicine for Major Disease Burden and Health Promotion”. Industry experts from Hong Kong, the Chinese mainland, Japan, Macau, the Netherlands, Singapore, Taiwan and the US

are sharing their insights at the conference on the bioactivity and life-nurturing function of Chinese medicine and present the latest research findings on the use of TCM in treating vascular and immunological diseases.

Health Forums and PresentationsA Chinese Medicine Health Public Forum co-ordinated by the Hong Kong Registered Chinese Medicine Practitioners Charitable Foundation will be held to extend knowledge and understanding of the practice and

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benefits of traditional Chinese medicine (TCM). This year’s forum takes the theme “Practical TCM Tips to Build up a Healthy Life”. During the event Chinese medicine practitioners will share practical tips on how to apply Chinese medicine to daily life.

The instructive theme continues with an educational display, co-organised by the Hong Kong Baptist University, which aims to increase the public’s understanding of the use of Chinese medicine as part of everyday health maintenance. Meanwhile at the Exhibitors’ Forum you can catch the latest products and services from some exhibitors.

The fair also offers plenty of oppor-tunities to make and extend contacts with a networking luncheon and networking reception.

The ever-popular HKTDC Food Expo and the HKTDC Hong Kong International Tea Fair which offer interesting prospects in related areas are taking place concurrently with the ICMCM, offering extra sourcing opportunities.

Register Now for Free AdmissionTrade buyers can now pre-register to get your admission badge through following channels:

• Website–registeratwww.hktdc.com/ex/ icmcm/05onorbefore25Julyforbuyersfrom outside Hong Kong to receive a free admission badge by mail; or

• SmartphoneInfoSite–downloadHKTDC Mobile at iPhone App Store, BlackBerry AppWorldorGooglePlay;or

• MobileInfoSite-hktdc.com/wap/icmcm/ T119

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INSIDEINDUSTRY

A leader in real-time PCR kits, ADT Biotech (altona DIAGNOSTICS) makes diagnostic technology more

accessible and efficient, benefiting hospitals, healthcare professionals and patients in this region

Altona DIAGNOSTICS off ic ial ly launched ADT Biotech Sdn Bhd, its new Asia Pacific regional headquarters in Kuala Lumpur, representing the reputable German biotech organization in the region. Building on a strong history of biotechnology research, development and innovation, including experience at the renowned Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, the founders of altona DIAGNOSTICS have also launched artus Malaysia Sdn Bhd in 2002, which was the key industry player for molecular diagnostics at the time and has achieved recognition by making the first diagnostic SARS kit available in the region.

ADT Biotech (altona DIAGNOSTICS) specializes in the development and commercialization of molecular diagnostic tests based on state-of-the-art real-time PCR (polymerase chain reaction) technology. The clinically proven, validated and standardized assays amplify and detect pathogen-specific DNA or RNA and benefit healthcare practitioners by delivering reliable and reproducible results while increasing efficiency, turnaround times and removing ambiguity from many diagnostic procedures.

ADT Biotech (altona DIAGNOSTICS) is the culmination of over 20 years of innovative achievements and was conferred BioNexus status by the Malaysian Biotechnology Corporation (BiotechCorp), a special recognition awarded to qualified local and international companies responsible for spearheading innovations in the field of biotechnology.

“We are very excited to mark the establishment of a strong direct presence in the Asia Pacific region, in addition to our European and US offices, in order to expand our R&D capabilities and provide high

German biotech innovator Altona Diagnostics launches BioNexus-certified regional hub in Malaysia: ADT Biotech Sdn Bhd

level technical support and training to our customers in the region,” said Dr. Finn Zedler, Managing Director, ADT Biotech Sdn Bhd.

“ADT is confident with our choice of Malaysia as the Asia Pacific regional headquarters due to i ts sc ient i f ic achievements and unique collaboration opportunities with leading Malaysian institutions in this field, as well as a conducive and dynamic business environment and a solid platform for our regional activities, in addition to the impressive level of support and dedication extended by BiotechCorp,“ he added.

“BiotechCorp is constantly seeking to validate and recognize companies such as ADT Biotech which bring a wealth of innovation, as well as research and development capabilities which benefit not just Malaysians but the global community,” said Yang Berbahagia Dato’ Dr Mohd Nazlee Kamal, Chief Executive Officer, BiotechCorp. “Altona Diagnostic’s global reputation and expertise in developing fast and accurate solutions for infectious disease detection, focusing on emerging pathogens, is admirable and we look forward

to continuously support their activities as a BioNexus status company.”

Dr Ulrich Spengler, founder of Altona DIAGNOSTICS, Germany, added: “As a pioneer in molecular diagnostics and the commercialization of real-time PCR, we look forward to working closely with Malaysian talent to make this technology more accessible to healthcare practitioners here in this region. Our collaborations with Malaysian institutions will be especially significant in global efforts such as our recently-announced strategic partnership with the Bernhard Nocht Institute for Tropical Medicine to develop a specimen bank dedicated to tropical and rare diseases. Malaysian expertise in this area would be invaluable and mutually beneficial exchanges of knowledge such as these bear great promise for the future.”

altona DIAGNOSTICS’ RealStar® PCR kits have been validated for a broad range of real-time PCR instruments, offering the broadest menu for infectious disease testing with the greatest flexibility to the diagnostic lab. RealStar® PCR assays are IVD-CE marked for diagnostic use.

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M icroscopists are invited to submit images to be considered for promotion of upcoming edu-

cation-focused, giant-screen film. FEI, a scientific instruments company,

has joined forces with National Geographic Cinema Ventures for its annual owners’ image contest. All FEI instrument owners are invited to submit their best images through September 22 to compete for inclusion in National Geographic promotional materials for its much anticipated 2013 giant screen film “Invisible Worlds.” And, for the first time, the image contest will include ASPEX and TILL Photonics microscope users as well.

“We are thrilled to be partnering with National Geographic on an exciting new film that will show audiences aspects of the world around them that are not visible to the naked eye,” stated John Williams, FEI’s vice president, corporate and strategic marketing. “A portion of the film utilizes

FEI launches “Explore the Unseen” image contest in partnership with National Geographic

electron microscopy to allow people to see the smallest of the small, from the tiniest living organisms to the atoms and molecules that ultimately compose everything we know. FEI is proud of the important work that our customers do and the images that they submit to the annual image contest. And we are extremely pleased to provide access to one of our newest microscopes and our skilled technical staff to help in the production of the film.”

Promotional materials will likely include a companion game, book, education guide and poster, which will also include images from FEI microscopes.

“We invite all FEI owners to submit their best images to be considered for inclusion in the film’s promotion material,” said Williams.

The top three images will be posted on the Nat Geo Movies Facebook page and the

Nat Geo Movies website. Winners will also receive prizes from FEI.

According to Williams, “Categories for this year’s image contest will be more consumer friendly, such as ‘The Natural World’, ‘The Human Body’, and ‘Around the House’.”

“We are also looking for images with a high ‘Yuck Factor’ that will generate interest from kids, as well as other generally interesting subjects like bacteria, cells, micro-invertebrates in water, or the inside workings of solar cells and electronics.” Williams adds, “We invite everyone to let their imaginations run wild for this year’s image contest.”

The National Geographic film, “Invisible Worlds,” debuts in the fall of 2013. For more information about the image contest, please go to: http://www.fei.com/2012-image-contest/.

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T he Biotechnology Industry Organization (BIO) thanked Representative Marcy Kaptur (D-Ohio) and 16 other original

cosponsors for introducing the Rural Energy Investment Act of 2012, which would reauthorize Farm Bill Energy Title programs, provide significant mandatory funding, and ensure eligibility for additional biorefineries and products, such as biobased products and renewable chemicals. BIO President & CEO Jim Greenwood released the following statement:

“The Farm Bill energy programs have produced a high rate of return for American taxpayers, in terms of viable projects funded and operating and new employment opportunities in rural areas. We will work with Representative Kaptur and other

S istemic Ltd. (“Sistemic”), a leading p rov ider o f mic roRNA-based problem-solving services and kit-

based products, has formed a customer relationship with Cytori Therapeutics (“Cytori”). Cytori will utilize Sistemic’s proprietary SistemQC™ technology platform in its U.S. cardiac cell therapy clinical trial to molecularly characterize adipose-derived stem and regenerative cells (ADRCs).

“Research has shown that within adipose tissue, as well as other cell sources like bone marrow, there are multiple distinct cell types that can contribute to efficacy,” commented Sistemic chairman and CEO Jim Reid. “Cytori selecting our SistemQC serves as another validation of our technology, particularly its flexibility to characterize a wide variety of cells for identity and potency, on a molecular level. We could not be more pleased to have reached this agreement with Cytori.”

The announcement was made at the 2012 Bio International Convention in

BIO applauds Representative Kaptur’s Energy Investment Act of 2012

Members of Congress to ensure that these successful programs continue to work.”

“I agree with Representative Kaptur that Farm Bill energy programs are working. The programs have had a tremendous positive impact in revitalizing rural America, helping new agricultural markets emerge, and reducing the need for direct payments to farmers. Through these programs, companies are unlocking private capital for construction of the nation’s first cellulosic and advanced

biofuel biorefineries; and farmers in 12 states are putting more than 160,000 acres of underutilized farmland back into production raising next generation energy crops. There has also been an explosion of renewable chemicals innovation, demonstration and early commercialization here in the United States, and Representative Kaptur’s bill would support its continued momentum.”

“The Farm Bill energy programs have produced a high rate of return for American taxpayers, in terms of viable projects funded and operating and new employment opportunities in rural areas. We will work with Representative Kaptur and other Members of Congress to ensure that these successful programs continue to work.”

Source: Business Wire

Cytori to utilize Sistemic’s SistemQC™ to strengthen understanding of mechanisms & support design of Next-Generation Cell Therapies

Boston, where Mr. Reid was moderating a panel on stem cell therapeutics featuring leaders from the industry at the Boston Convention Center.

“SistemQC will be incorporated into our clinical development to understand which cell types within our Celution® System’s autologous heterogeneous population

of ADRCs are the greatest contributors to efficacy,” said Douglas Arm, Ph.D., Senior Vice President Operations at Cytori. “With Sistemic’s novel technology, we can strengthen the mechanistic understanding of our cell output and at the same time support the design of next-generation cell therapies.”

Source: B3C newswire

57

INSIDEINDUSTRY

B osch Packaging Technology and Sartorius Stedim Biotech (SSB) announced a long-term global

partnership agreement at Achema 2012 in Frankfurt/Main, Germany. SSB is a leading international supplier of equipment and services for the development, quality assurance and production processes of the pharmaceutical and biopharmaceutical industry. The agreement between Bosch and SSB covers the mutual design and

<insert photo 1-PA-18420>

Bosch packaging technology and Sartorius Stedim Biotech introduce PreVAS

development of single-use filling solutions to be used on aseptic filling equipment from Bosch for final fill-and-finish operations of liquid pharmaceuticals. SSB will provide Bosch with pre-configured single-use filling transfer sets, consisting of bags, filters, tubing and connectors. Bosch will combine these sets with its aseptic filling and barrier isolation technology to form new systems for aseptic filling, and exclusively market, distribute and service these new filling systems under the Bosch brand.

Pre-validated, pre-assembled and pre-sterilized:

With the new product line PreVAS (Pre-Validated, Pre-Assembled, Pre-Sterilized), Bosch will supply its customers with highly cost-effective plug and play tools which provide additional flexibility for aseptic filling operations backed by comprehensive validation packages.

“By integrating SSB’s single-use technologies into our aseptic filling systems, we are expanding our product and service

portfolio in the area of fill-and-finish unit operations by an important component. With our joint expertise, we intend to develop configurable and customized single-use filling solutions and to provide strong validation and technical support,” Joachim Brenner, responsible worldwide for the Bosch Pharma Liquid portfolio and general manager at the Crailsheim plant, stated.

“ The pa r tne r sh ip w i th Bosch promotes the implementation of single-use technologies into critical applications such as final filling operations and strengthens the confidence in single-use technology,” Jean Marc Cappia, Vice President Fluid Management Technologies, SSB specified, and added: “Our customers from the pharmaceutical and bio-pharmaceutical industry are facing rising cost pressure and time constraints. By integrating single-use technology into fill-and-finish unit operations, they can handle smaller batches and product changeovers in a safe, economic and flexible way.”

CellCentric and ZoBio Enter into Partnership to Develop Lead Compounds against Epigenetic Drug Targets

Z oBio and CellCentric are pleased to announce that the companies are working together to discover lead

compounds against CellCentric’s portfolio of epigenetic therapeutic drug targets. ZoBio will use its proprietary TINS technology to screen its fragment library against targets nominated by CellCentric. Hit to lead and lead optimisation activities will be further supported by ZoBio’s biophysical and medicinal chemistry research services.

Dr. Gregg Siegal, Chief Scientific Officer at ZoBio said “We are clearly happy that CellCentric has chosen ZoBio as a partner in this challenging project. Epigenetics is an

exciting, yet challenging, field. We feel that our unique combination of biophysical and biochemical approaches yields significant advantages in developing small molecule inhibitors of these targets with optimal drug-like properties.”

Dr Anthony Brown, Scientific Director at CellCentric, said “The ZoBio TINS technology offers a unique opportunity to identify novel hit matter against our epigenetic drug targets. The interaction with ZoBio will allow us to expand the breath of our hit finding capabilities and will accelerate our on-going drug discovery activities. We are delighted to enter into this

agreement to screen against these novel and exciting epigenetic drug targets.”

Source: Business Wire

58

ONFERENCEC A L E N D A RC

3 – 4 AugustSingHealth Duke-NUS Scientific CongressSingaporeTel: +65 6377 8644Email: shsdn.scientificcongress@singhealth.com.sgURL: http://www.singhealthacademy.com.sg/sites/sdc

16 – 18 AugustInternational Conference & Exhibition of the Modernization of Chinese Medicine & Health Products 2012 Hong Kong Contact Person: Mr. Savi Au / Ms. Tessa LamTel: +852 2584 4333 Fax: +852 2824 0026 Email: icmcm.visitor@hktdc.org URL: www.hktdc.com/ex/icmcm/05

AUGUST 201221 – 24 August5th Annual Asia Pharmaceuticals Regulatory SummitSingaporeContact Person: Rita ParasurumTel: +65 6508 2401Email: Rita.Parasurum@ibcasia.com.sg URL: http://www.pharmaregulatoryasia.com/

21 – 22 AugustBioprocess InternationalShanghai, ChinaEmail: reg@ibcusa.comURL: http://www.ibclifesciences.com/BPIChina/overview.xml

23 – 24 August BioPharma Australasia Covnention Sydney, AustraliaContact Person: Robert Marten Tel: +61 2 9021 8808 Fax: +61 2 9281 5517 Email: robert.marten@terrapinn.comURL: http://www.terrapinn.com/conference/biopharma-australasia/

27 – 28 AugustAnnual Global Healthcare Conference (GHC 2012)Singapore Tel: +65 6327 0166 Fax: +65 6327 0162Email: info@globalhc-conf.orgURL: http://www.globalhc-conf.org/

28 – 30 August5th World Circulating Tumor Cells SummitSingapore Tel: +1 212 537 5898Email: info@hansonwade.comURL: http://ctcsummit-asia.com/

5 – 7 SeptemberHealth Positioned Food & Beverages Asia 2012Hong KongTel: +65 6508 2401 Fax: +65 6508 2407Email: register@ibcasia.com.sg URL: http://www.nutrafood-bevasia.com/index.php

5 – 7 SeptemberRoyan International Congress on Reproductive Biomedicine & Stem Cell Biology & TechnologyTehran, IranContact Person: Leila DaliriTel: +98 21 26301995Fax: +98 21 23562178 Email: info@royancongress.comURL: http://www.royancongress.com

10 – 11 September Proteins & Biopharma Asia Congress 2012SingaporeURL: http://www.biopharmasia-congress.com/

SEPTEMBER 201210 – 13 SeptemberSoutheast Asia Pharmaceutical Forum 2012SingaporeTel: +65 6508 2401 Fax: +65 6508 2407Email: register@ibcasia.com.sg URL: http://www.pharmaceuticalasia.com/

12 – 14 September4th Annual Partnerships in Clinical Trials AsiaShanghai, ChinaTel: +86 21 2326 3680 (China) +86 6508 2401 (All regions) Email: register@ibcasia.com.sgURL: http://www.iirusa.com/clinicaltrialsasia/event-welcome.xml

12 – 14 SeptemberPharma Strategic Sourcing & Outsourcing Asia 2012Shanghai, ChinaTel: +65 6508 2401 Fax: +65 6508 2407Email: register@ibcasia.com.sg URL: http://www.pharmasourcingasia.com/

21 – 23 SeptemberInternational Conference on SchizophreniaTamil Nadu, IndiaTel: + 91 44 2435 3079 Fax: + 91 44 2432 0605 Email: tours@icons-scarf.orgURL: http://www.icons-scarf.org/

26 – 27 September1st Malaysian Proteomics Conference (MPC) 2012Penang, MalaysiaTel: +609 767 2402/2403/2404Fax: +604 653 4803/+609 764 8673E-mail: mpc2012@usm.myURL: http://www.informm.usm.my/mpc2012/

28 – 29 September2012 2nd International Conference on Energy and Environmental Science (ICEES 2012)Phnom Penh, CambodiaEmail: icees@iacsit.orgURL: http://www.icees.org/

59

ONFERENCEC A L E N D A RC

1 – 2 October2nd Annual Next Generation Sequencing Asia CongressSingaporeTel: + 65 657 0 2208 Fax: +65 657 0 2209 Email: info@oxfordglobalasia.com.URL: www.ngsasia-congress.com

3 – 5 October3rd International Conference on Computational Systems-Biology and BioinformaticsBangkok, Thailand Contact Person: Kasaporn SukataTel: +66 2564 6700 ext. 3379-3382 Fax: +66 2564 6574 Email: Csbio2012@biotec.or.th URL: http://www.csbio.org

OCTOBER 2012

NOVEMBER 2012 DECEMBER 2012

7 – 11 OctoberThe 12th International Symposium on Dendritic CellsDeagu, KoreaTel: +82-2-557-8422Fax: +82-2-566-6087Email: dc@people-x.comURL: http://www.dc2012.kr/

10 – 12 OctoberBio Pharma- India Today to Future 2020Mumbai, IndiaTel: +971 4 60 91 555 Fax: +971 4 60 91 589 E-mail: info@fleminggulf.comURL: http://www.fleminggulf.com/conferenceview/Bio-Pharma-India---Today-to-Future-2020/274

15 – 17 OctoberImmunogenicity for Biopharmaceuticals & Biosimilars Asia 2012SingaporeTel: +65 6508 2401 Fax: +65 6508 2407Email: register@ibcasia.com.sgURL: http://www.immunogenicityasia.com/

15 – 18 October7th Annual Summit: Branded Generics Strategy AsiaSingaporeTel: +65 6508 2401 Fax: +65 6508 2407Email: register@ibcasia.com.sg URL: http://www.generics-asia.com/

27 – 28 October2012 International Conference on Life Science and Engineering (ICLSE 2012)Hong Kong Contact person: Mr WuEmail: iclse@cbees.org URL: http://www.iclse.org/index.htm

27 – 30 October3rd International Conference on Stem Cells and Cancer (ICSCC-2012): Proliferation, Differentiation and ApoptosisNew Delhi, IndiaContact person: Dr. Sheo Mohan Singh Email: icscc2012@gmail.comURL: http://www.icscc.in/

1 – 2 NovemberInternational Conference on SPEECH, IMAGE, BIOMEDICAL & INFORMATION PROCESSING 2012 (SIBIP 2012)Punjab, IndiaContact person: Shivani MalhotraEmail: shivani.malhotra@chitkara.edu.inURL: http://sibip2012.chitkara.edu.in

5 – 7 NovemberBiologics World China 2012Shanghai, ChinaTel: +65 6493 2093 Fax: +65 6270 2792Email: info@imapac.comURL: http://www.imapac.com/index.php?page=BiologicsWorldChina2012

7 – 8 November4th International Conference on Science & Technology (ICSTIE)Penang, MalaysiaContact person: Azlina Mohd MydinTel: +604 3823373Fax to +604 3822766Email: icstie2012@gmail.comURL: http://www.icstie.com

21 – 23 NovemberSingapore International Conference on Dengue and Emerging Infections SingaporeContact person: Shirley TayTel: +65 6618 2235 Fax: +65 6886 9536 Email : secretariat@events360.com.sgURL: http://stopdengue.sg/conference2012/

24 – 25 November2012 International Conference on Future Bioengineering (ICFB 2012)Bangkok, Thailand Contact person: Miss FengE-mail: icfb@cbees.orgURL: http://www.icfb.org/index.htm

26 – 27 NovemberBioPharma India Convention 2012Contact Person: Huisan SohTel: +65 6322 2770Fax: +65 6223 3554Email: huisan.soh@terrapinn.comURL: http://www.terrapinn.com/conference/biopharma-india-convention/

6 – 7 December2nd International Conference on Biomedical Engineering and Assistive Technologies Punjab, India Contact person: Dr Dilbag SinghTel: +91 98884 92132 Telefax: +91 181 2690932/ 2690320 Email: beats2012@nitj.ac.in URL: http://www.beats2012.org/Beats

12 – 13 DecemberBiofest-2012, Biotechnology International Conference and Exhibition Hyderabad, India Email: biofest2012@brightice.org URL: http://www.brightice.org

22 – 23 December2012 3rd International Conference on Nanotechnology and Biosensors (ICNB 2012)Kuala Lumpur, MalaysiaContact person: Mr. Lee Email: icnb@cbees.orgURL: http://www.icnb.org/

22 – 23 December2012 4th Journal Conference on Bioscience, Biochemistry and Bioinformatics (JCBBB 2012 4th) Kuala Lumpur, Malaysia E-mail: ijbbb@vip.163.com URL: http://www.ijbbb.org/jcbbb/4th/

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Editorial and Advisory Board

Editorial Board Members

• Albert YU Hong Kong Biotechnology Organization, Hong Kong

• Calvin HO National University of Singapore, Singapore

• CHEN Chien-Jen Academia Sinica, Taiwan & National Taiwan University, Taiwan

• Franco ORSUCCI University College London Cambridgeshire NHS Foundation Trust, Cambridge, UK

• George Guo-Qiang CHEN Tsinghua University, Beijing, China

• Kevin WANG University of Florida, USA

• KUNCHITHAPADAM Swaminathan National University of Singapore, Singapore

Advisory Board Members

• HONG Hai Nanyang Technological University, Singapore

• Jia-Rui WU Shanghai Institute for Biological Sciences, CAS, Shanghai, China

• Marvin NG DN Venture Partners LLP, Singapore

• PAN Shen Quan National University of Singapore, Singapore

• QU Dong Yu Chinese Academy of Agricultural Sciences, Beijing, China

• Salah ALKHALLAGI King Abdulaziz Medical City, Saudi Arabia

• Yi-Xue LI Shanghai Jiaotong University, Shanghai, China

• Lei ZHOU Singapore Eye Research Institute, Singapore National University of Singapore, Singapore

• Roger W BEUERMAN Singapore Eye Research Institute, Singapore National University of Singapore, Singapore Duke-NUS, SRP Neuroscience and Behavioral Disorders, Singapore

• Sang Yup LEE Korea Advanced Institute of Science and Technology, Korea

• Sarada BULCHAND Duke-National University of Singapore Graduate Medical School, Singapore

• Shangwei WU Kingmed Center for Clinical Laboratory, China

• Suzanne KADEREIT University of Konstanz, Germany