Diapositiva 1

Dr. Jos M. Milln, PhDDeputy Director of CIBERERUniversitary Hospital La Fe, Valencia, SpainBarriers and Challenges in Rare Diseases ResearchCentre for Biomedical Network Research on Rare Diseases (CIBERER)A model of cooperative and translational research on rare diseases

DublinMarch 26, 2012

Research in Rare Diseases in Spain Historial Overview1996. Creation of CISAT (Centre for the Research of the Toxic Oil) in the Institute of Health Carlos III (ISCIII)2000. Rare Diseases are included by ISCIII as a Main Topic for its Research Programme.2001. CISAT becomes CISATER (Centre for the Research of the Toxic Oil and Rare Diseases). Creation of SIERE (Service of Information on Rare Diseases in Spanish). 2003. RETICs (Networks for Thematic Research): REpIER, INERGEN y RECGEN (One epidemiological network and two genetic research networks on RD. CISATER is then named IIER (Institute for Research in Rare Diseases2006. CIBERER (Centre for Biomedical Network Research on Rare Diseases)

Prioritary Biomedical Research TopicsCNIO: National Centre for Oncology ResearchCNIC: National Centre for Cardiovascular ResearchCIBERS:CIBERNED: Neurodegenerative disordersCIBERES: Respiratory disordersCIBERHED: Hepatic and digestive disordersCIBEROBN: Obesity and NutritionCIBERDEM: Diabetes and associated metabolic disordersCIBERBBN: Bioengineering, Biomaterials and NanomedicineCIBERER: Rare DiseasesCIBERESP: Epidemiology and Public HealthCIBERSAM: Mental Health

2009. Strategy for Rare Diseases of the National Health SystemMinistry of Health and Social PolicyCoordinator: Prof. Francesc Palau

Needs:InformationPrevention and Early DiagnosisHealth and Social CareTherapyResearchTrainingLack of knowledge, lack of informationDeficient or inexistent health registries for many rare diseases and difficult coding according to the ICD system of classificationDifficulties for epidemiological studies

VisibilityTo identify the current human and information resources To set up registries for each rare disease and for rare diseases as a global problemTo ascertain the medical/ economical burden of rare diseasesBeware of Dr. !!

EpidemiologyBarriers in Rare Diseases Research

The budget for biomedical research in Spain is low compared to other EU countries (0.9% GDP)The budget for rare diseases is low compared to common diseases

To stimulate future R&D projects within the Health Strategic Actions To promote the priorization of research projects on rare diseasesTo create, maintain and improve necessary structures, facilities and human resources

Basic and Clinical ResearchNatural History, Physiopathology, Genetics, Disease Models...Barriers in Rare Diseases ResearchLack of interest of the Pharma industry (too much investment for too low economical benefit)Very few emerging small companies interested inNot many laboratories working in therapies for rare diseases

To promote interest and financial support from the Public Health System and Pharma enterprisesCollaboration with Pharma Industry and BiotechsTo promote research in orphan drugs - advanced therapies (gene-based therapy and cell therapy)

TherapyBarriers in Rare Diseases ResearchIn Spain there is not a formal specialty in Clinical GeneticsRare diseases are not a topic in Universities, Medicine Schools...Students and scientist are more prone to common diseases (Cancer, AIDS, Alzheimer dis., Cardiovascular dis...)Difficulties in making a carrier in genetics and rare diseases

Creation of the specialty in Clinical Genetics (for physicians, biomedical sciences, psicology...(AEGH and CIBERER)Courses, masters, academic topics devoted to rare diseases

TrainingBarriers in Rare Diseases ResearchWhy research on rare diseases is needed?Social reasons Medical reasonsScientific reasons

March 26th , 2012Rare Diseases ResearchSupranational collaboration European Networks of CoE, ECN European policy: fostering national plans European platforms & infrastructures Patient empowermentMultidisciplinary andIntegrative approach National Centres of Expertise (CoE) Clinical investigation/Basic research National research networks Databases, registries, biobanks, epidemiological surveillance Pharmaceuticals and biotechsSocialfactorPolitical factorHealthcaresystemSocietyFinancial factorTraining factorHuman factorResearch groupsCIBERER: An integrative proposalMarch 26th , 2012CIBERER is a public consortium set up at the initiative of the Institute of Health Carlos III (ISCIII) to act as a reference to coordinate and foster research into Rare Diseases in Spain.

CIBERER groups clinical and basic researchers promoting Cooperative Research. The knowledge generated is translated from the laboratory to clinical practice, and vice versa: Translational Research.CIBERER provides strategic coordination, human resources and materials as well as a collaborative environment where synergy proper to high multidisciplinary and complementary research potential can be developed.The CIBERER has large human resources - over 700 persons, made up of its own staff of 159 CIBERER contracted researchers, the rest of the members of the groups being scientists and technicians attached to CIBERER.

53% of our personnel are PhD associate researchers. Centre for Biomedical Network Research on Rare Diseases (CIBERER)March 26th , 2012Intramural Biomedical Projects in Rare Diseases (PIBER)Paediatric and Developmental MedicineSupport Platforms for Research into Rare Diseases (PITER)Inherited Metabolic MedicineGenetic MedicineManagement Office

Scientific Director Governing BoardPermanent CommissionExternal Advisory Scientific CommitteeManagement Committee(Coordinators)Associated Clinical Groups Research Programmes: Thematic Medical ProgrammesIntramural Projects and Support PlatformsNeuro-sensorialPathologyInherited Cancer and Related SyndromesEndocrine MedicineMitochondrial MedicineOrganization Chart of the CIBERER March 26th , 2012CIBERER units are organized into seven Research Programmes:

Cooperative research in the field of rare diseases

Reseach ProgrammesGenetic Medicine 16 research groupsInherited Metabolic Medicine 11 research groupsMitochondrial Medicine 8 research groupsPediatric and Developmental Medicine 8 research groupsNeurosensorial Pathology 7 research groupsEndocrine Medicine 4 research groupsInherited Cancer and Related Syndromes 6 research groupsMarch 26th , 201260 Research Groups 29 Consorted Institutions 7 Research ProgrammesThe centre encloses clinical and basic researchers promoting Cooperative Research in Rare Diseases. It is a Centre with an innovative network structure: offers opportunities of research actions and public-private collaboration. Internal Structure of CIBERERThe knowledge generated is translated from the laboratory to clinical practice Translational Research

March 26th , 2012During its 5 years of existence, the CIBERER has allowed increasing the research capacity of its scientific groups and has increased the knowledge about Rare Diseases. CIBERER Programmes have:Joined and increased the Cooperation between basic and clinical unitsIncreased the Research on Rare DiseasesFostered the Participation of groups in the CIBERERs programmesEstablished Institutional RelationsPromoted and Disseminated the activities of groups Fostered the International Cooperation opportunities of groups

Network core facilitiesCooperative research in the field of rare diseases

BIERBioInformatica de Enfermedades RarasMarch 26th , 2012Cooperation with the Spanish Biotech Stakeholders Association (ASEBIO)Collaboration with specific preclinical research actors Agreement with Medina Foundation: non-profit publicprivate partnership between Merck Sharp and Dohme and public institutions focused on the discovery of new compounds and innovative therapies for unmet medical needs Examples of intramural cooperative research projects

Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Raya et al. CIBERER Units 710 & 745. Nature. 2009 May 31

Transplantation of histocompatible allogeneic epidermal stem cells: Development of an effective clinical resource for patients with dystrophic epidermolysis bullosa. INTRA/08/714,1.

Gene therapy in Dyskeratosis congenita INTRA/08/757,1. CIBERER Units 757 & 710

Evaluation of the immune response and oxidative stress in patients affected by Gaucher disease subjected to different forms of therapeutic treatment. INTRA/08/752.2. CIBERER Units 752 & 719

CIBERER member of Innovative Medicaments working group CIBERERs therapeutic research

March 26th , 2012The approach is to establish scientific collaborations with experts from others academic research groups, biotech and pharmaceutical companies interested in testing their compounds and their panels of target screens in specific rare diseases models.

CIBERER experimental models network resources:

91 animal models for the study of rare diseases: Mouse, Zebrafish, Drosophila, Medaka, C. elegans.

59 cells models for the study of rare diseases: HeLa, 3T3, SH-S5SY neuroblastoma cells, fibroblasts, COS cells, lymphoblast cells, astrocytesExperimental models in rare diseases: towards preclinical research

Example of animal models:McArdle disease (Pygm) X-linked adrenoleukodystrophy (Abcd1) Charcot-Marie-Tooth type 4A (Gdap1)Retinitis pigmentosa (Cerkl)Down syndrome (Dyrk1a, others)Lafora disease (malin, laforine)Etc.March 26th , 2012

2007 -2011: an increase of the scientific collaboration and productivity by the CIBERER groupsEvolution of intramural collaboration - CIBERER 2000-02 and 2006-08March 26th , 201218Intramural collaboration CIBERER 2010

2007 -2011: an increase of the scientific collaboration and productivity by the CIBERER groupsMarch 26th , 201219

Collaborative network of CIBERER groups with other Spanish institutions (240)Collaborative network of CIBERER groups with other international institutions(742)

2007 -2011: an increase of the scientific collaboration and productivity by the CIBERER groupsMarch 26th , 201220Outcomes: increase on the number and quality of papers in RDPublications output between 2005 - 2010Documents200520062007200820092010Original Article241216336396321405Biography2Correction231152Editorial Material55128815Letter101312221518Meeting Abstract54731266913990Proceedings Paper7972Review161027212536Cited267239382448368461% cited/total81,474,773,384,870,681,2Total328320521528521568

March 26th , 201221

Evolution of the papers distribution of CIBERER groups based on JIF (Journal Impact Factor) parametersOutcomes: increase on the number and quality of papers in RDMarch 26th , 201222

Go raibh maith agat Thank you

More Information:www.ciberer.esinfo@ciberer.es (+34) 96.339.47.89

A model of Cooperative Research on Rare DiseasesFebruary 18th , 2011