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4th 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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
OUR HISTORY
1999 -2000 2000-02 2005 2006 2012 2013 2009-2015
*Shroff G et al. Annals of Neurosciences. 2015;22(3).
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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%
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
TREATMENT PLAN FOR 101 CP PATIENTS
*Caudal route if required, or deep muscle spinal cord injection 1 ml weekly in T1 & T2
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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.
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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.
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
MAJORITY OF PATIENTS SHOWED IMPROVEMENT AFTER THE THERAPY*
*Shroff G et al. J Transl Med. 2014;12(1):318
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
AT END OF T1, MAJORITY OF PATIENTS HAD AN IMPROVEMENT BY AT LEAST ONE GRADE
IN GMFCS
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
BEFORE TREATMENT
SPECT scan of a cerebral palsy patient (grey - normal; red, pink and white - above normal; green, light/dark blue, black -hypoperfused)
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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)
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
AFTER THERAPY NONE OF THE PATIENTS HAD EPILEPTIC ATTACKS MULTIPLE TIMES
A DAY
Out of 101, 59 patients were affected for epilepsy
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
AFTER THERAPY, 97.5% OF PATIENTS SHOWED AN
IMPROVEMENT IN NFS BY AT LEAST ONE LEVEL
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
BEFORE
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
AFTER
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
REPORT
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
BEFORE AFTER
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
69% OF THE PATIENTS SHOWED AN IMPROVEMENT IN COGNITIVE
SKILLS
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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.
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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.
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
OUR MISSION
TO SEE HUMAN EMBRYONIC STEM
CELLS AVAILABLE GLOBALLY AS THE FIRST LINE OF TREATMENT FOR MANY OF MANKIND’S WORST AFFLICTIONS
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