The track record of clinical trials involving human embryonic stem cells (hESCs) is worse than miserable. A dozen years ago, it was thought that for sure by now in 2010 hESCs would be used in all kinds of regenerative medicinal applications. Instead, they remain stalled at the gate while other types of stem cells are being used to produce all kinds of intereting results. In the blog post It’s a long way to stem cell treatment I discussed how the clinical trial of Geron’s proprietary hESC-based product GRNOPC1 was being delayed for the second time in August 2009 because of FDA caution(ref). That trial, still being delayed, involves the use of hESCs for treating severe spinal cord injuries.
It is very tempting to blame lack of progress in development of hESC therapies on government banning of funding of most embryonic stem cell research during the Bush era. I personally think the ban was a terrible idea, anti-science and anti-humanistic. While the ban has been a factor, however, I do not think it had a major impact on worldwide progress in hESC research. And, simply put, other kinds of stem cells have turned out to be more exciting and more easy to work with. The stubborn challenges associated with hESC therapies appear to be 1. possible immune system rejection or reactions because the cells are not derived from the patient (the cells are not autologous), and 2. assuring that the stem cells differentiate into the desired target cell types and only those types. More-specialized patient-derived stem cells like haemopoietic and mesenchymal stem cells do not run the risk of immune system rejection and their differentiation can be directed more easily. And, autologous induced pluripotent stem cells (iPSCs) seem to be able to do everything that hESCs can do without immune system rejection.
There was news last week that GRNOPC1 is emerging again in a new clinical context, this time for treating Alzheimer’s disease. The report Geron to Study Its hESC Product in Alzheimer Disease with University of California in Gen states “Geron and researchers from the University of California have decided to work together to assess the company’s human embryonic stem cell (hESC) product, GRNOPC1, for Alzheimer disease. The work will be jointly funded by the firm and a university discovery research and training grant. — Geron and the University of California team will now evaluate GRNOPC1 in models of Alzheimer disease. The study is designed to assess whether memory shows recovery after transplantation of GRNOPC1. — The research will be led by Frank M. LaFerla, Ph.D., director of the Institute for Brain Aging and Dementia at the University of California, Irvine.”
The interest follows in large part from promising mouse studies. “There are striking parallels between recent data on mouse stem cells in Alzheimer’s disease models and what we know about GRNOPC1(ref).” Dr. LaFerla and his colleagues published a research report in August 2009 entitled Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. That report cited data demonstrating “that defects in memory were improved by glial cells derived from mouse neural stem cells transplanted into the hippocampus of rodent models of Alzheimer disease. — GRNOPC1 contains the precursors to human glial cells, which matured and repaired the lesion site in rodent models of spinal cord injury. Additionally, the improvement in memory and the increase in synaptic density observed after injection of neural stem cells were found to be mediated, at least in part, by the neurotrophic factor BDNF, which is secreted from the transplanted cells. GRNOPC1 has been found to secrete BDNF as well as other neurotrophic factors(ref).” “Taken together, our findings demonstrate that neural stem cells can ameliorate complex behavioral deficits associated with widespread Alzheimer disease pathology via BDNF(ref).”
If and when GRNOPC1 is to be used in a clinical trial for Alzheimer’s disease is yet to be determined as, apparently, whether and when the clinical trial of GRNOPC1 for severe spinal cord injury will be resumed. The great original glow of hESC-based therapies is now dim and continues to fade while the prospects for other stem cell therapies seem to grow brighter and brighter.