4 th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff

4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff


HUMAN EMBRYONIC STEM CELL THERAPY IN CHILDREN WITH CERBRAL PALSY

Dr. Geeta Shroff Founder and Medical

Director, Nutech Mediworld


CONDITIONS TREATED

Cell Culture Technology

Diabetes Type 1 & 2

Genetic Disorders

Skin

Bed Sores

Burns

Wounds

Cardiac , & liver

Disorders

Spinal Cord Injury

Auto-immune

Disorders

Musculo-skeltal

Disorders

Neurological disorders

hESC Therapy

Vision


CONVENTIONAL DERIVATION

In-Vitro Fertilization Blastocyst Inner Cell Mass(Embryoblast)

Isolated Cells

Pluripotent

Cells cultured in Lab

Research Only (Animal Protein Contamination)

Mouse Feeder Cells

Sperm

Blastocoele

Throw-away fertilized ovum

Other Products

Fetal Bovine Serum

TrophoblastEgg


HESC: WE CULTURE THEM DIFFERENTLY

Neuronal cell

Ready to use Cell Cultures

Re-incubated

Store

d IncubatedNon-neuronal cell

No Feeder Layer

No Animal Product

128- Cell

8- Cell2- Cell

4 Cell16- Cell 32-

Cell

Re-incubated Store

d

Ready to use Cell Cultures

64- Cell

Day0 1 2 3 4 5 6


TECHNOLOGY HIGHLIGHTS

Patented technology1,2

In-house cultured hESC from a Single Fertilized Ovum

Non- contaminated Free of animal products

stable cell lines upon 4000 passages3

Viable and ready-to-use product form Simple, Cost-effective and Scalable No immunosuppressants needed No significant adverse event in over 13 years of

therapeutic usage

1. http://patentscope.wipo.int/search/en/WO20071416572. Shroff G, International Journal of Recent Scientific Research3. Paper communicated


OUR HISTORY

1999 -2000 2000-02 2005 2006 2012 2013 2009-2015

*Shroff G et al. Annals of Neurosciences. 2015;22(3).


CEREBRAL PALSY IN CHILDREN

o Prevalence of CP around the world ranges from 1.5 to more than 4 per 1,000 live births1

o Caused by permanent, non-progressive brain lesion

1 http://www.cdc.gov/ncbddd/cp/data.html


SYMPTOMS

Stiff or floppy posture ,

Excessive lethargy or irritability/

High pitched cry, behavioral issues

Weak suck/ tongue thrust/

feeding difficulties, speech difficulties, visual

problems

Poor head control, hypertonia or hypotonia


CEREBRAL PALSY: THE DISEASE

o Motor, Cognitive and/or Motor-Congnitive Disorder

o 35% -50% of children with CP also have seizure disorder and some level of mental retardation

o May have learning disabilities and vision, speech, hearing, or language problems


AVAILABLE CONVENTIONAL TREATMENTS

Medicines

Botox, Intrathecal Baclofen- control

muscle spasms and seizures,

Glycopyrrolate -control drooling

Pamidronate -may help with osteoporosis Surgery may help To relieve muscle tightness Straightening of different twists or unusual curvatures of leg muscles Improve the ability to sit, stand, and walk

No treatment can cure it 100%


STUDY DESIGN

PATIENTS

AGE GROUPS

TREATMENT

PARAMETERS

101 Patients suffering from CP were included

<2yrs, 2-4yrs, 4-6yrs, 6-12 & 12-18 yrs.

Study divided in four treatment

phases. T1, T2, T3 & T4

SPECT SCANSGMFCS

NFS SCOREADVERSE EVENTS Safety evaluation was done by

measuring adverse events in all treatment phases


TREATMENT PLAN FOR 101 CP PATIENTS

*Caudal route if required, or deep muscle spinal cord injection 1 ml weekly in T1 & T2


STUDY CHARACTERISTICS

Most patients were males (71.4%) aged up to 18 yr

Total treatment days were: T1 - 60 days T2 - 30 days T3 - 33 days T4 - 29 days

Data for all the patients was validated by Moody International and Quality Austria Central Asia Pvt Ltd.


GMFCS –INTERNATIONAL SCORING SYSTEM

Provides description of the child’s motor function

Gives an idea of what support the child might need

Is classified according to age The scores are from 1 to 5 with 5 being the

worst.


MAJORITY OF PATIENTS SHOWED IMPROVEMENT AFTER THE THERAPY*

*Shroff G et al. J Transl Med. 2014;12(1):318


AT END OF T1, MAJORITY OF PATIENTS HAD AN IMPROVEMENT BY AT LEAST ONE GRADE

IN GMFCS


BEFORE TREATMENT

SPECT scan of a cerebral palsy patient (grey - normal; red, pink and white - above normal; green, light/dark blue, black -hypoperfused)


AFTER TREATMENT (8

MNTHS)

SPECT scan of a cerebral palsy patient (grey - normal; red, pink and white - above normal; green, light/dark blue, black -hypoperfused)


NUTECH FUNCTIONAL SCORES (NFS)

A 32 point positional and directional scoring system to evaluate patient with CP*

Each symptom is categorized into 5 ordinal grades (1, 2, 3, 4, 5) in BAD → GOOD direction

Can assess abilities related to sensory system such as feeling and controlling bladder and bowel excretion, hearing, and seeing and cognitive abilities like feeling hotness or coldness and understanding a “command”

Assessed speech and epilepsy outcomes also based on NFS

*Shroff et al. International Archives of Medicine. 2015; 8: 117


NFS FOR EPILEPSY

Description Score

Multiple times/ day 1

1-2 times/ day 2

1-2 times/ alternative day 3

1-2 times/ week or occasionally

4

Less frequent than in 4 5

Of 101 CP Patients, 59 had Epilepsy


AFTER THERAPY NONE OF THE PATIENTS HAD EPILEPTIC ATTACKS MULTIPLE TIMES

A DAY

Out of 101, 59 patients were affected for epilepsy


NFS FOR SPEECH

Description Score

Dependent on alternate communication system

1

Disarticulate and incomprehensible 2

Disarticulate but often comprehensible 3

Slurred but comprehensible 4

Normal speech 5

Of 101 CP Patients, 93 had Speech Problems


OF 93 AFFECTED PATIENTS, 27 HAD NORMAL SPEECH AT THE END OF

THERAPY

Out of 101, 93 patients were affected for speech

None of the patient was Non-verbal after the hESC Therapy


CORTICAL VISUAL IMPAIRMENT (CVI)

Visual loss due to disturbance in the posterior visual pathway or the visual cortex

Common in patients with CP

No medications or surgical therapies available except rehabilitation therapy


MEASUREMENT OF CVI USING NFS The level of visual impairment was assessed

using NFS:

Description Score

No perception of light 1

Perception of light present 2

Can identify objects but the images are blurred and have finger counting ability depending on age

3

Can see objects up to a distance of 25 cm

4

Normal vision 5

Of 101 CP Patients, 40 had CVI


AFTER THERAPY, 97.5% OF PATIENTS SHOWED AN

IMPROVEMENT IN NFS BY AT LEAST ONE LEVEL


BEFORE


AFTER


REPORT


BEFORE AFTER


69% OF THE PATIENTS SHOWED AN IMPROVEMENT IN COGNITIVE

SKILLS


THE AES WERE MILD AND RESOLVED WITHOUT SEQUEL

Treatment Phase (N)

Adverse Events (AEs)

Number and Percentage of

Patients Affected

n(%)

T1 (N=91) Swelling, Itching, Fever and Throat infection

9 (9.9%)

T2 (N=66) Diarrhea, Body pain 2 (3%)

T3 (N=38) Diarrhea 1 (2.6%)

T4 (N=15) No adverse events 0

N= Total number of patients in treatment phase n= No of patients affected with ADEs

NO TERATOMA OR IMMUNE REACTION WERE OBSERVED

NO IMMUNOSUPPRESSANTS WERE GIVEN TO PATIENTS


CONCLUSION

o The size of the hESCs used in our study is less than 1

µm facilitating them to cross the blood brain barrier

o The changes in SPECT scan depict that these cells

migrated to the affected area and showed an improvement in perfusion

o GMFCS scores show that the therapy has improved the overall well being of the patients.

Most patients affected with CP were able to improve

their quality of life


CONTD…

o hESC therapy provided to 101 patients of CP has benefitted patients by reducing their symptoms of epilepsy and improving their speech.

o At the end of T1, out of 59 patients affected with epilepsy, 18 patients had shown complete disappearance of epileptic episodes and out of 93 patients whose speech was affected , 48 patients became completely normal.

o 18 patients had stopped their anti epileptic medications

o Almost all the children (39 of 40) showed improvement in vision by at least one grade. Of the 8 blind patients, all showed improvement in vision (greater than 2). More than half of the patients regained normal vision at the end of the study after receiving hESC therapy


PUBLICATIONS1. Shroff G, Das L. Human Embryonic Stem Cell Therapy in Cerebral

Palsy Children with Cortical Visual Impairment: A Case Series of 40 Patients. J Cell Sci Ther. 2014;5(6):1.

2. Shroff G. A novel approach of human embryonic stem cells therapy in treatment of Friedrich’s Ataxia. Int J Case Rep Images. 2015;6:261–266.

3. Shroff G, Gupta R. Human Embryonic Stem Cells in the Treatment of Patients with Spinal Cord Injury. Annals of Neurosciences. 2015;22(4).

4. Shroff, G. Das, L. Use of Human Embryonic Stem Cells (hESCs) in the Treatment of Glaucoma. International Journal of Medical and Pharmaceutical Case Reports. 2015; 4(3):2394-109X.

5. Shroff G, Barthakur JK. Safety and Efficacy of Human Embryonic Stem Cells for the Treatment of Cerebrovascular Accident: A Case Series. Global Journal of Medical Research. 2015. In Press.

6. Shroff G. Treatment of Lyme Disease with Human Embryonic Stem Cells: A Case Series. J Neuroinfect Dis. 2015; 6:167.

7. Shroff G. Human Embryonic Stem Cells in the Treatment of Spinocerebellar Ataxia: A Case Series. J. Clin. Case. Rep. 2015; 5:1.

8. Shroff G (2015) Human Embryonic Stem Cells in the Treatment of Patients with Duchenne Muscular Dystrophy. J Neurol Res, 5, 186.


CONTD…9. Shroff G, Gupta A, Barthakur J. Therapeutic potential of human embryonic stem

cell transplantation in patients with cerebral palsy. J Transl Med. 2014;12(1):318.

10. Shroff G. Role of Anesthetists in Human Embryonic Stem Cells Transplantation in Patients with Spinal Cord Injury. In Press

11. Shroff G, Barthakur JK. Safety of Human Embryonic Stem Cells in Patients with Terminal Conditions. Annals of Neurosciences. 2015;22(3).

12. Shroff G, Barthakur JK, Mohan P, Mahajan H. Single Photon Emission Computed Tomography Scan as a Diagnostic Tool in Children with Cerebral Palsy Treated with Human Embryonic Stem Cells. Journal of Nuclear Medicine and Therapy. 6 (3), 1.

13. Nutech Functional Score (NFS), a New Scoring System to Assess the Level of Impairment in Patients with Cerebral Palsy. International Archives of Medicine. 2015; 8: 117

14. Shroff G. Establishment and Characterization of a Neuronal Cell line derived from a 2-cell Stage Human Embryo: Clinically Tested Cell-based Therapy for Neurological Disorders. International Journal of Recent Scientific Research 2015;6(4):3730-8.

16. Shroff G, Gupta R, Makhija LK. Evaluation of Wound Healing Ability with Human Embryonic Stem Cells in Patients with Non-Healing Wounds: A Case Series. Journal of Pigmentary Disorders 2015; 2:7.


CONTD…..17. Shroff G. Clinical Effect of Human Embryonic Stem Cells Therapy in Two

Cases of Cerebral Palsy. J Neurol Res. 2015;5(3):230-232

18. Shroff G. Use of Human Embryonic Stem Cells in the Treatment of Age-Related Macular Degeneration. J Clin Exp Ophthalmol 2015; 6:446.

19. Shroff G, Barthakur JK, Mohan P, Mahajan H. Single Photon Emission Computed Tomography Scan as a Diagnostic Tool in Children with Cerebral Palsy Treated with Human Embryonic Stem Cells. J Nucl Med Radiat Ther 2015, 6:3.

20. Shroff G. Human embryonic stem cells (hESCs) in the treatment of emphysematous COPD: a case report. Clinical Case Reports 2015, 3(7): 632-634.

21. Shroff G. Human Embryonic Stem Cell for the Treatment of Multiple Sclerosis. Case report international. 2015. In Press

22. Barthakur IK, Shroff G. Natural Selection of Gender of the Baby at Conception: Proposing a Scientific Hypothesis. Science Journal of Public Health 2015; 664-668

23. Shroff G. Nutech Functional Score (NFS), a New Scoring System to Assess the Level of Impairment in Patients with Cerebral Palsy. International Archives of Medicine. 2015; 8.

24. Shroff G, Agarwal P, Mishra A, Sonowal N. Human Embryonic Stem Cells in Treatment of Spinal Cord Injury: A Prospective Study


OUR MISSION

TO SEE HUMAN EMBRYONIC STEM

CELLS AVAILABLE GLOBALLY AS THE FIRST LINE OF TREATMENT FOR MANY OF MANKIND’S WORST AFFLICTIONS


THANK YOU

Documents

4 th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff