StemCells, Inc. Announces Completion of Enrollment of Its First Cohort in Their Chronic Spinal Cord Injury Trial

StemCells, Inc. announced on December 15, 2001 that the first cohort of the Company’s Phase I/II clinical trial in chronic spinal cord injury have been successfully transplanted with the Company’s proprietary HuCNS-SC neural stem cells. This is a landmark clinical trial that has a unique design. What makes this clinical trial unique is the implantation of patients with progressively decreasing severity of spinal cord injury that are treated three sequential cohorts. The first cohort of patients all have spinal cord injury classified as AIS A, which is the most severe type of spinal cord injury as defined by the American Spinal Injury Association Impairment Scale or AIS.

Stephen Huhn MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, Inc. made this statement: “We are extremely pleased with our progress in this innovative trial. Having completed dosing of the AIS A cohort, screening for AIS B patients, who have a less severe, incomplete type of spinal cord injury, can now begin. Of course, our first priority is to assess safety in each patient, but we will also be evaluating trial patients for changes in sensation, motor and bowel/bladder function.”

Martin McGlynn, President and CEO of StemCells Inc added, “I am also pleased to announce that, in consultation with the clinical team at Balgrist Hospital (University of Zurich), the Company has decided to open enrollment for the remainder of the trial to patients living in the United States and Canada. We have received a large number of inquiries from patients in both countries, and hopefully this decision will come as good news to the spinal cord injury community, who were greatly disappointed by Geron’s recent decision to discontinue its spinal cord injury trial. We remain optimistic about the prospect of being able to demonstrate safety and clinical utility of our cells in this devastating condition, and are committed to funding our spinal cord injury program until such time as we can come up with a definitive outcome.”

The Phase I/II clinical trial of StemCells, Inc.’s HuCNS-SC purified human adult neural stem cells is designed to assess both safety and preliminary efficacy of this cell line in the treatment of spinal cord injuries. Twelve patients with thoracic (chest-level) neurological injuries at the T2-T11 level are planned for enrollment. The first three patients all have injuries classified as AIS A, in which there is no apparent neurological function below the level of spinal cord injury. The planned second and third cohorts will consist of patients who have spinal cord injuries classified as AIS B and AIS C, which are less severe than AIS A spinal cord injuries and show at least some preservation of sensory or motor function. This trial will assess safety of the cell line and treatment efficacy based on specific criteria. These clinical criteria include changes in sensation, motor and bowel/bladder function. Prior to implanting the next cohort, data from previous cohorts will be reviewed by an independent Data Safety Monitoring Committee.

All patients will receive HuCNS-SC cells through direct transplantation into the spinal cord and will receive initial doses of medicines that suppress the immune system to ensure that the implanted cells do not elicit inflammation or are instantly rejected by the immune system. However, these drug treatments are temporary, since the central nervous system is surrounded by a blood-brain barrier than prevents the immune system from rejecting transplantations into the central nervous system. Temporary treatment with immunosuppressive drugs are necessary at the beginning of the procedure because the implantations breach the blood brain barrier and until this breach heals, the immune system has access to the implantation, but after the breach heals, immunosuppression is no longer necessary. Implanted patients will be evaluated regularly in the period after the transplant in order to monitor and assess the safety of the HuCNS-SC cells and the implantation procedure, and to determine if there are any neurological changes in the patients. The Company intends to follow the effects of this therapy long-term, and a separate four-year observational study will be initiated at the conclusion of this trial.

The trial is being conducted at Balgrist University Hospital, University of Zurich, a world leading medical center for spinal cord injury and rehabilitation. This institution has a global reputation for providing some of the highest quality examinations, treatments and rehabilitation opportunities to patients with serious musculoskeletal conditions. The clinic owes its leading international reputation to its unique combination of specialized medical services. The hospital’s carefully balanced, interdisciplinary network brings together under one roof medical specialties including orthopedics, paraplegiology, radiology, anesthesiology, rheumatology, and physical medicine.

Induced Pluripotent Stem Cells Produce Pigs That are Superior Model Systems for Medical Research

Rodents are the standard laboratory model system for testing the safety of treatments, chemicals and other medically important protocols and devices. Rodents share an immune system that is very similar to the primate immune system, and also share many other biological features with primates. However, all the drugs we ingest usually make a stop at the liver where they are chemically modified, and this modification step differs from rodents to humans. Some drugs are processed in very similar manners in rats, mice and humans, but many other drugs are processed quite differently. In such cases, rodents make poor model systems for how those drugs might affect human patients.

Another case where rodent models are less than exemplary is cancer studies. Experiments on rodents and rodent-derived cell lines have provided vital insights into the genetics, cell biology and molecular biology of cancer, carcinogens, or compounds that cause cancer in living organisms, have very different effects in rodents and humans. For example, some components in coffee appear to be carcinogenic in rodents, but in humans moderate coffee consumption may reduce the risk of cancer.

Another field of research trends to show very different results in humans and rodents and that field is stem cell research. Induced pluripotent stem cells (iPSCs), which are embryonic-like stem cells made from adult cells though genetic engineering techniques, very effectively cause tumors in rodents. However, in 2010, University of Georgia scientists Steve Stice and Franklin West introduced 13 pigs that might show the way toward new regenerative therapies. These pigs have been the subjects of some experiments with iPSCs and the astounding result is that adult-cell-sourced stem cells (iPSCs) don’t form tumors in these pigs.

West, an animal science researcher and assistant professor in the UGA College of Agricultural and Environmental Sciences said: “Pluripotent stem cells have significant potential for stem cell therapies . . . However, tests in mice often resulted in tumor formation that frequently led to death.” Such robust tumor formation raised concerns about the safety of iPSCs and any cells derived from iPSCs. However, to date, the vast majority of these safety tests have been done in rodent models. Given the rodents can show different results in carcinogenesis tests (a test that determines the tendency of a chemical to cause cancer) relative to humans, West and Stice wondered if these differences as translated into tumor tests with iPSCs.

To address this concern, West and Stice, and their research colleagues examined tumor formation in pigs that were actually made from iPSCs. The results were striking. According to West, “Brain, skin, liver, pancreas, stomach, intestine, lung, heart, kidney, muscle, spleen and gonad tissues from all 11 pigs tested showed no evidence of tumors.” The absence of tumor formation in these pigs suggests that iPSCs can safely incorporate into tissues without causing the formation of tumor.

The potential of such animals as model systems for medical purposes is not lost on these scientists. Steve Stice, a Georgia Research Alliance Eminent Scholar in the College of Agricultural and Environmental Sciences, said: “Being able to safely use iPSCs without the potential of causing tumors is essential for this promising stem cell therapy to become a viable treatment option . . . We now have graduate students working on making neural cells from the human and pig stem cells to help further the studies. The human stem cells were effective in a rodent model for stroke, but rodent studies are not rigorous enough to start human clinical trials.”

There are over 700 drug treatments that have gone to human clinical trials for stroke alone based on safety tests that were done on rodents. However once these drugs were brought to clinical trials, they failed all safety tests. These pigs, however, are much more similar to humans when it comes to drug processing and tolerance. Such animals are much better model systems to study strokes than rodents.

West is leading a cooperative project between the UGA Regenerative Bioscience Center and stroke researchers at Georgia Health Sciences University. “This project will improve the speed and efficiency of treatment development for stroke and many other conditions and potentially reduce the number of nonhuman primates used in research,” he said. In addition to this collaboration, Stice and West have now bred the pigs produced from iPSCs and have demonstrated that the stem cells did form germ cells (eggs and sperm), and their genes were passed to their offspring. These data opens the door for better animal-sourced tissue for human regenerative medicine such as islet cells that produce insulin for diabetic patients.

Using iPSC technology, the UGA Regenerative Bioscience Center is working with researchers at Emory University to make pigs whose cells from the pancreas demonstrate decreased rejection in human treatments. Stice noted, “The next step would be to put these pig insulin-producing cells into other animals, potentially dogs or cats suffering from diabetes—to see if it will produce insulin for them without being rejected . . . So, it’s moving forward. Never as fast as we like, but it’s moving.”