Transcript hESC Therapy - Conferences

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
Spinal Cord
Injury
Cell Culture
Technology
Diabetes
Type 1 & 2
Autoimmune
Disorders
Genetic
Disorders
Musculoskeltal
Disorders
Skin
Bed Sores
hESC Therapy
Burns
Wounds
Vision
Neurological
disorders
Cardiac , &
liver
Disorders
4th 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
4th 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
Ready to use Cell Cultures
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/WO2007141657
2. Shroff G, International Journal of Recent Scientific Research
3. Paper communicated
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
OUR HISTORY
1999 -2000
Accidental
Discovery of
hESC
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 -,
Publication
s in peer
reviewed
journals
*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
o
Prevalence of CP around
the world ranges from 1.5
to more than 4 per 1,000
live births1
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
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
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
101 Patients suffering from CP were
included
AGE GROUPS
<2yrs, 2-4yrs, 4-6yrs, 6-12 & 12-18 yrs.
TREATMENT
Study divided in four treatment phases.
T1, T2, T3 & T4
PARAMETERS
SPECT SCANS
GMFCS
NFS SCORE
ADVERSE
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
T1
(N=91, 8 Weeks)
Test dose
(0.05 ml sc on
forearm)
to check
hypersensitivity
0.5ml IM once daily followed
by 1.0 ml IV twice every 7
days*
T2
(N= 66, 4 Weeks)
After 3-6 months gap
of T1
0.5ml IM once daily
followed by 1.0 ml IV twice
daily every 7 days*
T3
(N= 38, 4 Weeks)
After 3-6 months gap
of T2
0.5ml IM once daily followed
by 1.0 ml IV twice daily every
7 days
T4
(N=15, 1 Month)
After 12 months gap
of T3
Same+ Additional 1ml IV
dose
*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*
12
11
1010
Number of Patients
10
10
9
8
9
8
8
8 8
7
7
6
6
5
6
5
5
5
5
4
4
4
3
3
3
2 2 2
2
1
000 0
3
2
1
33
2
1
00
0
1
00
0
0000
0
1
2
3
4
5
1
Before Treatment
2
3
4
After Treatment
GMFCS Scores
5
< 2 YRS
2-4 YRS
4-6 YRS
6-12 YRS
*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
120
100
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
2-4 YRS
4-6 YRS
7.4
6-12 YRS
0
12-18 YRS
Age (Yrs)
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
None of the patient
was Non-verbal
after the hESC
Therapy
Out of 101, 93 patients were affected for speech
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
30
27 (67.5%)
Number of Patients
25
20
16 (40%)
15
10 (25%)
10
8 (20%)
9 (22.5%)
Before
treatment
6 (15%)
After
treatment
5
2 (5%)
1 (2.5%)
0 (0%)
0 (0%)
0
1
2
3
NFS Scores
4
5
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
62.9
All Parameters
81.7
Smiling
80.3
Recognition/Awareness
28.8
Symptoms
Problem solving
72.8
Eye contact
56.1
Toilet Training
68.3
Feeding
61.8
Defense Mechanism
49.5
Speech
78.9
Aggression
47.4
Daily Living skills
74.5
Following commands
0
10
20
30
40
50
60
70
80
N (%)
4th 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(%)
T1 (N=91)
Swelling, Itching, Fever and Throat
infection
9 (9.9%)
NO TERATOMA OR IMMUNE REACTION
Diarrhea,
Body pain
T2 (N=66)
WERE
OBSERVED
NO IMMUNOSUPPRESSANTS WERE
GIVEN TO PATIENTS
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
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
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 (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 AgeRelated 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): 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
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
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff
THANK YOU
4th International Conference and Exhibition on Cell & Gene Therapy August 10-12, 2015, London l Dr. Geeta Shroff