Patrick Cox Features ISCO's Stem Cell Parkinson's Study

Patrick Cox blogs about ISCO's success in primate study (data presented at American Academy of Neurology Annual Meeting, March 20th 2013).  Reproduced with the permission of P.Cox.

ISCO Shows Functioning Parthenogenic Stem Cells in Parkinson's Chimp Study

International Stem Cell Corp. (OTCBB: ISCO) has announced the most important experimental results in the history of the company. Last week, the company confirmed that these nonembryonic stem cells can, in fact, become part of a host primate and function as normal cells.

Now I'm really feeling guilty because this story deserves a lot more attention than I can give it today. Nevertheless, ISCO presented the results of a blinded chimpanzee Parkinson's study at the American Academy of Neurology's 65th annual meeting on March 20.

There's been a lot of skepticism about the potential of human parthenogenic stem cells (hpSCs) for several reasons. First of all, they don't develop naturally into adult cells such as the neuronal cells that were used in this study. Unlike regular cells that have the DNA of both the mother and the father, hpSC DNA consists of two copies of the mother's genome, so they have to be provoked to become specific cell types.

As a result, these hpSCs, which come from immature ova gathered during routine in vitro fertilization procedures, cannot develop into fetuses. Obviously, this is a big plus for those who oppose the use of embryonic stem cells. It raised the possibility, however, that cells derived from hpSCs would not function as normal cells for therapeutic purposes.

We now know that hpSC-derived neuronal cells will engraft, became part of the chimps they were given to and produce the dopamine needed to prevent the symptoms of Parkinson's disease. This is powerful evidence of hpSC efficacy, though I'm not at all surprised by these results.

You should read the press release, which states:

"‘This pilot study represents a first essential step in bringing cell-based therapies for Parkinson's disease to clinical trials,’ commented co-author of the study Evan Y. Snyder, MD, Ph.D., director of Stem Cells and Regenerative Biology Program at Sanford Burnham Medical Research Institute. “These placebo-controlled studies were designed to demonstrate the viability, fate and functional efficacy of the stem cell-derived neural cells after implantation to the brain. Highly pure populations of neuronal cells were differentiated from human parthenogenetic stem cells (hpSC) according to the protocol developed by International Stem Cell Corp. and recently published in the Nature Publishing Group's Scientific Reports. “The studies employ MPTP-lesioned African green monkeys and 6-OHDA-lesioned rats, the principal models used to study Parkinson's disease. The duration of the primate study was four months and the rodent study six months. In the nonhuman primate model, behavioral endpoints were assessed with Parkinsonian scores. These scores, based on a standardized rating scale, were recorded by observers blinded to whether the primates were in the treatment or control group. Observations were done twice per day, five days per week. In the rodent model, behavioral improvement was assessed using the cylinder test, amphetamine and apomorphine-induced rotation tests. Cell engraftment, viability and phenotype of the implanted cells were determined histologically at the end of the studies. Tumorigenicity and safety of the therapy was assessed at the end of both the rodent and primate studies by gross necropsy, and brain histology. “The primate study consisted of eight asymptomatic monkeys which have the pathology of the disease, low levels of dopamine induced by bilateral injections of the neurotoxin MPTP and lack clinical symptoms. Four of the monkeys were transplanted with hpSC-derived neuronal cells, two monkeys sham transplanted with an equivalent volume of cell-less media thus serving as the placebo control group and two healthy monkeys serving as a positive control. Behavioral endpoints were recorded to evaluate possible adverse effects. “Subsequent to implantation of the neuronal cells, all monkeys in the treatment group had higher levels of dopamine in the brain compared with the control group. Additionally, the rats in the treatment group showed gradual improvements in motor symptoms consistent with cells survival, engraftment and dopamine release. No adverse events, including dyskinesia, deformations, tumors or overgrowth, were observed in the rat or monkey treatment groups. Overall, these results provide evidence to support the hypothesis that hpSC-derived neuronal cells can be safe and have a disease modifying effect. These results, although preliminary, are a strong indication that our approach to Parkinson's disease can succeed. "‘These results are pivotal for our preclinical Parkinson's program showing, as they do, that the hpSC-derived neuronal cells can potentially ameliorate the behavioral symptoms without triggering dyskinesias. This data form the foundation of our discussions with the FDA as we move toward our IND in 2013,’ said Dr. Ruslan Semechkin, principal investigator of this study, head of R&D for International Stem Cell Corp. and Member of the American Academy of Neurology. “These results will be presented and discussed at the 65th American Academy of Neurology annual meeting, one of the world's most important annual events for neurologists and neuroscience professionals and the largest such international meeting of its kind, with more than 12,000 attendees at last year's meeting.”

Obviously, the company intends to bolster this study with larger primate studies before going into human studies, hopefully early next year. The importance of hpSC therapies, however, shouldn't be overlooked. Not only do they provide a solution to many people's ethical problems with embryonically derived stem cells, they represent an entirely different path to regenerative medicine.

As you know, BioTime (AMEX: BTX) recently consolidated Geron's stem cell IP. BioTime is now the undisputed leader in embryonic and induced pluripotent stem cells. ISCO, however, owns the parthenogenic space. It uses methods of differentiation and cell production that are unique to its own platform. In fact, far more information is available about those technologies in this journal article of Nature's Scientific Reports.

Ultimately, when the company has created its bank of cell lines to match most of the human species, it will be able to provide off-the-shelf therapeutic cells for many conditions that would otherwise require immune suppression or iPS cells. This is a big deal, but it's also in the future. The Parkinson's disease target is ideal for ISCO because there is no immune rejection behind the blood-brain barrier where these cells are required. This enables a path to revenues much sooner than the cell line strategy.

I'll have a lot more on this development in the future. Already, these results have generated more attention in the scientific press than the company has ever before garnered. That will increase as more information is released.

Also, by the way, the company's hpSC cosmetics line, Lifeline Skin Care, is getting serious attention in the beauty and anti-aging press. Products have recently been featured in Elle and Prevention magazines as well as other forums.

Yours for transformational profits,

Patrick Cox