Embryonic stem cells in cerebral palsy – results of clinical study from India

by Alexey Bersenev on January 11, 2015 · 5 comments

in neurology

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One clinical study, which was released 2 weeks before Christmas holidays captured my attention (but not attention of mass media). One of the most scandalous Indian “stem cell tourism” clinic Nutech Mediworld published(!) results of the study, which evaluates embryonic stem cell transplantation in children with cerebral palsy. Yes, you’re reading it correctly – embryonic stem cells in children! Now, I have no idea how this study was approved by Independent Ethics Committee (as stated in the paper) and how this manuscript passed peer review of Journal of Translational Medicine, but here is the fact – study is done and results are published. I think, we should at least read it, try to analyze it (it’s not easy!) and maybe discuss it. Before we dive into the study, I’d like to give you a little bit of background.

Geeta Shroff – a director of Nutech Mediworld – is a highly controversial and highly criticized by “westerners” figure in “stem cell tourism”. She is “a retired obstetrician and self-taught embryonic stem cell practitioner”, who used to be skeptical about sharing data with peers:

Dr. Shroff does not share data, has not submitted to peer review (she’s said she has “no peers”) and has performed no controlled clinical trials. While patients call her a saviour, other researchers call her a quack, a fraud or names even less flattering.

Well, seem like she changed her mind lately. I remember, that many “critics” refused to believe that actual embryonic stem cells (ESC) were used by Nutech. They thought that Nutech used term “embryonic” for fetal cells, derived from aborted material. But, according the paper it’s real single ESC line, derived from preimplantation embryo post IVF.

Let’s move to the study. As I mentioned above, study protocol was approved by Ethics Committee. Also, it was reported to “National Apex Body” (I don’t know what is it, but sounds like something on government level). Yet another interesting fact – the last author of the paper is a government worker (Ministry of Home Affairs, Government of India). I’d like to remind you that this is not the first “embryonic stem cell study” from India. So, I think, one thing we have to realize is that if these kind of studies could be “shocking” and “hard to imagine” in US or Europe, it could be “normal” and totally acceptable for India or some other countries. Also, we have to realize that reporting of some particular number of patients (“cherry picking”?), treated in one particular “stem cell clinic” is very different from well designed clinical study or trial. We have no way to check how information, presented in the paper is accurate, since it’s not a registered trial and there is no (as far as I understand) oversight from any agency.

Next, I’d like to touch ESC product composition, which was used in kids with cerebral palsy. The authors did not bother much with differentiation of ESC into mature cells. In fact, transplanted ESC were Oct4+, SSEA3+, Nanog+, Sox+, betaHCG+, CD34+, Nestin+, GAF+ and NeuN+. So, it was a great mix of undifferentiated ESC and neurally induced progenitors. There is a reference to Shroff’s patent in the paper. If we look at this patent (which btw covers everything – all types of ESC derivatives and all kind of diseases), we can see that ESC product contains at least 40% of undifferentiated cells:

…in one embodiment, the portion of undifferentiated stem cells will be no more than about 80% of the total population of cells. In another embodiment, the portion of undifferentiated stem cells will be no more than about 40% of the total population of cells.

ESC progeny in the product are not characterized and could be hematopoietic, neural, mesenchymal, hepatic… Cells were infused and injected multiple times via all possible routes: intramuscular, intravenously, “intra-caudal”, as eye drops, as nasal spray, retro-bulbar, as oral or ear drops. Since, there was no immunosuppression, researchers check hypersensitivity to ESC product via skin probe before starting a treatment. One more interesting thing – the cells were cryo-stored in pre-filled syringes at -20C. There is no viability data in the paper.

91 children were included in the “study” with age from 1 month to 18 years with different degree and course of disease. The authors noticed functional improvement in all ages and starting scores of disease, based on functional scales (GMFCS-E & R). Also, they indicate improvement in cognition. Of course, we cannot make solid conclusions about efficacy, since it was not randomized and controlled trial. About 10% of patients had adverse events, such as swelling, itching, fever, chest congestion and others. However, there is no information about long-term safety and, especially, about such important potential complication as ESC-related excessive tissue growth. According the paper, about half of patients were not followed more than 3-6 months after the first treatment (did not return for 2nd and 3rd phases of treatment).

Of course, this “study” causes a lot of questions on every level – from ethical approval (without any pre-clinical animal studies) and study design to cell product characterization and clinical outcome. What puzzles me is that, apparently, Indian government agencies, as well as independent ethics committee were aware of the study and did not see any problem with it. I’d assume that Nutech itself did not see any problem with experimentation on children (for money!), because they had previous experience with ESC-based treatments of adults. Unfortunately, we cannot learn a lot from this study simply because of its design and lack of valuable information in the paper. I think, we as community should be aware of such “studies”, because it is a part of “cell therapy” or “stem cell therapy” or even “stem cell therapy industry”. What do you think of all this, guys?

{ 5 comments… read them below or add one }

Frances Verter January 21, 2015 at 10:41 am

The same month that this study appeared in print, Dec. 2014, the Times of India has twice reported that Indian federal authorities are tightening their enforcement of stem cell regulations…

The Indian FDA has shut down two private cord blood banks for not being licensed:
http://timesofindia.indiatimes.com/city/pune/2-cord-blood-banks-in-the-dock-for-violating-norms/articleshow/45624405.cms

The Indian DCGI has stopped “stem cell therapy” at Chaitanya Hospital:
http://timesofindia.indiatimes.com/city/pune/City-hospital-told-to-stop-stem-cell-treatment-for-violating-trial-norms/articleshow/45611429.cms

What is the net picture… that enforcement is increasing, or that enforcement is very uneven??

Reply

Dr Paramjit Dhot January 23, 2015 at 9:22 pm

The Indian Drugs and Cosmetics Act, clearly mentions the requirements of Cord Blood Banks, which need a licence before starting operations.It is monitored by the state FDA and approved by the Drugs Controller General of India.
Lifecell International is the largest, most accredited and started operations in 2004. It has more than 1,25,000 Cord blood units stored with 30 retrievals , 21 for Thallassaemia ,5 for Cerebral Palsy done in US FDA approved study in Duke’s University, and 4 for leukaemias with successful results
The regulatory authorities have clamped down on mushrooming of clinics doing unethical clinical trials and operation of Cord Blood Banks without licencing

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Zara Eriksen March 3, 2015 at 4:41 pm

Journal of Translational Medicine, publish sooo much c… I don’t understand how they still exist.

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rajani October 1, 2015 at 2:45 am

Dear all my father is fully paralyese and even not able to talk. I want such kid toy computer through which he can make words what he want say.
please help me out
Thanking You

Reply

SATISH TOTEY January 14, 2016 at 11:49 pm

Alexey,
Really surprised to see that such papers could be published in JTM. Apparently, while reading this paper you feel that data is managed and manipulated. How Independent Ethics Committee allowed to recruit patient of 1 month old? This independent ethics committee is stage managed and their own and not approved by DCGI. Apex committee cannot give them any approval. I bet. What is Home Ministry person is doing here when he has very little to contribute. Must be managing politically. I was one of the expert team member of a committee constituted by Indian Council of Medical Research (ICMR) for fact finding mission of this company in 2004-5. This company has political blessings and still going strong without any action from DCGI. Tragedy is that this company is very close to ICMR office. In India, we have several such companies that are currently offering unproven stem cell therapies and regulatory body is turning blind eye. It is unfortunate.

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