Biotechnology company StemCells, Inc., said that it has commented on the PLoS Medicine article published online February 17, 2009 describing a patient who developed “brain tumors” (glioneuronal neoplasms) after undergoing repeated transplants of “fetal neural stem cells” in Russia starting in 2001.
The company said it wishes to state that, after careful review of the information available, the particular circumstances of this unfortunate case are neither comparable nor relevant to the ongoing clinical development of HuCNS-SC ® cells, the company’s proprietary human central nervous system stem cell product candidate.
Based on the article and references cited therein, StemCells understands that the transplants in the case comprised an uncharacterized and poorly defined mixture of cells from multiple donors. It is unclear what preclinical safety testing was done, if any, on these cells. In contrast, the company’s HuCNS-SC cells comprise a highly purified, well characterized, neural stem cell product that has undergone rigorous preclinical safety testing, including testing for tumorigenic potential. To date, there has been no evidence of abnormal cell growth in several thousand test animals. In addition, the HuCNS-SC cells entered a Phase I clinical trial in 2006 under an IND authorized by the FDA and StemCells has been able to compile and analyze over two years of extensive human safety data. There has been no evidence of abnormal cell growth in any of the patients in this recently completed clinical trial, the transplantations have been well-tolerated and there have been no significant safety or toxicity concerns. In December 2008, the company received authorization from the FDA to initiate a Phase I clinical trial in a second indication.
The report in PLoS, Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient, describes the development of multifocal glioneuronal neoplasms along the spinal nerves and brain stem in a 13-year-old patient who underwent repeated transplantation procedures in an attempt to treat ataxia-telangiectasia (A-T). A-T is a progressive neurodegenerative disorder known to have an increased risk of developing cancer. According to the report, the patient underwent three separate transplants between 2001 and 2004 in an undisclosed hospital in Moscow. The patient was diagnosed in Israel with these tumors in 2005, and surgery was performed on the spinal growths in 2006. The surgically removed tissue was consistent with a low-grade glianeuronal neoplasm. The article reports a careful analysis that indicates the growths originated from donor cells derived from two or more tissue sources. The report notes that the child remains stable after the 2006 surgery and that further intervention has not yet been indicated.
This case appears to be a cautionary reminder of the importance of conducting clinical research using cells that have been tested for safety in animal studies and in accordance with standards designed to ensure high scientific, clinical, regulatory, and ethical integrity.
Stephen Huhn MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, said: “It is the company’s practice to conduct clinical research with recognized expert investigators at highly reputable institutions with experience conducting experimental trials, and even then only after receiving regulatory and ethics board approvals from well informed and sophisticated hospitals and regulatory authorities.
“The outcome in this case reported in PLoS needs to be understood in its proper context. The case involved a diagnosis that has a known increased risk of cancer, and a patient who underwent repeated cell injections eight years ago using multiple donor sources and who had uncertain medical follow-up between transplants. “It would be unfortunate and a disservice to the field of cellular therapy, and those conducting organized research, if results from isolated and uncontrolled transplants were to color people’s perceptions of the prospects of cell transplantation for the treatment of serious neurological disorders.”
The authors of the PLoS report acknowledge the risk of any medical procedures and conclude that “extensive research into the biology of stem cells and in-depth preclinical studies, especially of safety, should be pursued in order to maximize the potential benefits of regenerative medicine while minimizing the risks.” The company concurs with this view.
