4 th 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 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
CONDITIONS TREATED Spinal Cord Injury Cell Culture Technology Diabetes Type 1 & 2 Autoimmune Disorders Genetic Disorders Musculoskeltal Disorders Skin Bed Sores h. ESC Therapy Burns Wounds Vision Neurological disorders Cardiac , & liver Disorders 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
CONVENTIONAL DERIVATION Sperm Egg Trophoblast Blastocoele In-Vitro Fertilization Throw-away fertilized ovum Inner Cell Mass (Embryoblast) Blastocyst Isolated Cells Pluripoten t Other Products Fetal Bovine Serum Mouse Feeder Cells Research Only (Animal Protein Contamination) Cells cultured in Lab Disadvantages Antigen-antibody reactions Teratomas formed Immunosupressants required Chromosomal instability 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
HESC: WE CULTURE THEM DIFFERENTLY Day 0 2 - Cell 1 4 Cell 2 8 - Cell 3 4 5 6 16 - Cell 32 - Cell 64 - Cell 128 - Cell Neuronal cell Re-incubated Store Re-incubated No Feeder Layer No Animal Product Incubated Nonneuronal cell d Store d Ready to use Cell Cultures 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
TECHNOLOGY HIGHLIGHTS Patented technology 1, 2 In-house cultured h. ESC from a Single Fertilized Ovum Non- contaminated Free of animal products stable cell lines upon 4000 passages 3 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/WO 2007141657 2. Shroff G, International Journal of Recent Scientific Research 3. Paper communicated 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
OUR HISTORY 1999 -2000 Accidental Discovery of h. ESC 2000 -02 Safety and Efficacy Studies* 2005 100 Patients Treated 2006 Patent Applied 2012 1000 Patients Treated CSR released for 6 diseases 2013 Evidence Accepted by Regenerativ e Medicine Committee 2009 -2015 Patents granted -, Publications in peer reviewed journals *Shroff G et al. Annals of Neurosciences. 2015; 22(3). 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
CEREBRAL PALSY IN CHILDREN o o Prevalence of CP around the world ranges from 1. 5 to more than 4 per 1, 000 live births 1 Caused by permanent, non-progressive brain lesion 1 http: //www. cdc. gov/ncbddd/cp/data. html 4 th 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 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
CEREBRAL PALSY: THE DISEASE o o o Motor, Cognitive and/or Motor-Congnitive Disorder 35% -50% of children with CP also have seizure disorder and some level of mental retardation May have learning disabilities and vision, speech, hearing, or language problems 4 th 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% 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
STUDY DESIGN PATIENTS 101 Patients suffering from CP were included AGE GROUPS <2 yrs, 2 -4 yrs, 4 -6 yrs, 6 -12 & 12 -18 yrs. TREATMENT Study divided in four treatment phases. T 1, T 2, T 3 & T 4 PARAMETERS SPECT SCANS GMFCS NFS SCORE ADVERSE EVENTS Safety evaluation was done by measuring adverse events in all treatment phases 4 th 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 T 1 & T 2 4 th 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: T 1 - 60 days T 2 - 30 days T 3 - 33 days T 4 - 29 days Data for all the patients was validated by Moody International and Quality Austria Central Asia Pvt Ltd. 4 th 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. 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
MAJORITY OF PATIENTS SHOWED IMPROVEMENT AFTER THERAPY* 12 11 10 10 Number of Patients 10 9 8 8 8 7 7 6 6 5 5 5 4 4 3 3 2 2 2 1 000 0 1 33 2 1 0 2 3 2 1 00 5 4 3 2 0 10 3 4 Before Treatment 1 00 5 0 1 2 3 After Treatment 4 GMFCS Scores 0000 5 < 2 YRS 2 -4 YRS 4 -6 YRS 6 -12 YRS *Shroff G et al. J Transl Med. 2014; 12(1): 318 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
AT END OF T 1, MAJORITY OF PATIENTS HAD AN IMPROVEMENT BY AT LEAST ONE GRADE IN GMFCS 120 100 92. 9 90. 5 92. 6 100 Worse N (%) 80 No Change 60 Better 40 20 0 0 < 2 YRS 7. 1 9. 5 7. 4 2 -4 YRS 4 -6 YRS 6 -12 YRS 0 12 -18 YRS Age (Yrs) 4 th 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) 4 th 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) 4 th 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 4 th 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 4 th 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 4 th 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 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
NORMAL SPEECH AT THE END OF THERAPY None of the patient was Non-verbal after the h. ESC Therapy Out of 101, 93 patients were affected for speech 4 th 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 4 th 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 4 th 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 30 27 (67. 5%) Number of Patients 25 20 16 (40%) 15 10 10 (25%) 8 (20%) 9 (22. 5%) Before treatment 6 (15%) After treatment 5 2 (5%) 1 (2. 5%) 0 (0%) 0 1 2 3 NFS Scores 0 (0%) 4 5 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
BEFORE 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
AFTER 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
REPORT 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
BEFORE AFTER 4 th 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 All Parameters 62. 9 Smiling 81. 7 Recognition/Awareness 80. 3 Symptoms Problem solving 28. 8 Eye contact 72. 8 Toilet Training 56. 1 Feeding 68. 3 Defense Mechanism 61. 8 Speech 49. 5 Aggression 78. 9 Daily Living skills 47. 4 Following commands 74. 5 0 10 20 30 40 50 60 70 80 N (%) 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff 90
THE AES WERE MILD AND RESOLVED WITHOUT SEQUEL Treatment Phase (N) Adverse Events (AEs) Number and Percentage of Patients Affected n(%) T 1 (N=91) Swelling, Itching, Fever and Throat infection 9 (9. 9%) NO TERATOMA OR IMMUNE REACTION Diarrhea, Body pain WERE OBSERVED T 2 (N=66) NO IMMUNOSUPPRESSANTS WERE GIVEN TO PATIENTS 2 (3%) T 3 (N=38) Diarrhea 1 (2. 6%) T 4 (N=15) No adverse events 0 N= Total number of patients in treatment phase n= No of patients affected with ADEs 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
CONCLUSION o The size of the h. ESCs 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 therapy has improved the overall well being of the patients. Most patients affected with CP were able to improve their quality of life 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
CONTD… o h. ESC 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 T 1, 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 h. ESC therapy 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
PUBLICATIONS 1. 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 (h. ESCs) in the Treatment of Glaucoma. International Journal of Medical and Pharmaceutical Case Reports. 2015; 4(3): 2394 -109 X. 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. 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. 4 th 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. 4 th 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 (h. ESCs) in the treatment of emphysematous COPD: a case report. Clinical Case Reports 2015, 3(7): 632634. 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 4 th 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 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
THANK YOU 4 th International Conference and Exhibition on Cell & Gene Therapy August 10 -12, 2015, London l Dr. Geeta Shroff
Скачать презентацию 4 th International Conference and Exhibition on Cell
2b2124eb4657f8c86b8a812c88837a32.ppt