Neural stem cells (NSCs) to be used in chronic human spinal cord injury trial
The discovery of stem cells in the CNS capable of producing neurons in adults overturned the long-held belief that the only neurons a human would ever possess were those provided early in development. The dogma prior to the discovery of NSCs held that the brain and spinal cord were a very static organ with little endogenous repair mechanisms or plasticity. This is clearly not true. In fact new neurons and glia are produced on a continuous basis within the CNS. This discovery emerged from the work of Sally Temple who described multipotent, self-renewing progenitor and stem cells in the subventricular zone of the mouse brain in 1989 and Brent A. Reynolds (StepAhead's scientific director) and Samuel Wiess who were the first to isolate neural progenitor and stem cells from the adult striatal tissue including the subventricular zone in 1992.
NSCs have shown great promise in repairing spinal cord injuries and damage caused by degenerative disease or stroke. Perhaps one of the most appealing features of NSCs is they are native to the CNS. They originate and mature within the CNS. That fact alone hints that these cells may be more appropriate for CNS repair compared to adult stem cells that originate in other parts of the body, as for example bone marrow or adipose derived stem cells. NSCs have the characteristics of stem cells in general, including the ability to proliferate continuously after they are isolated from the brain. Thus quantities of NSCs large enough to be therapeutically useful in human repair efforts can be achieve fairly readily. In Vivo and in vitro NSCs are multipotent, meaning that they can give rise to all the cell types residing in the brain, including glia and neurons.
After two decades of animal experimentation it is clear that NSCs when implanted into the damaged CNS can effect a good deal of repair by replacing lost cells, both neurons and glia and reestablish neuronal circuitry. In addition, NSCs migrate to regions that are damaged to not only reconstruct the damaged area but also help protect distressed cells by secreting growth factors and forming direct cytoplasmic connections (gap junctions) with the troubled cells. This activity prevents much of the cell death that would otherwise occur. Experiments thus far have shown no evidence that NSCs transplanted into the CNS are likely to cause tumors to form (a concern about any cell type that can undergo unlimited proliferation)
Research efforts by a number of laboratories have now demonstrated that introducing NSCs into a damaged animal spinal cord can produce substantial recovery of function lost after spinal cord injury. Recent animal experiments demonstrate that NSCs can produce relays which in turn restores some function even if the damaged neurons fail to regenerate. In addition, at least some of the loss of function due to spinal cord injury is due to the death of myelin surrounding the long tract axons, which are otherwise intact. NSCs can differentiate into new myelinating cells (oligodendrocytes) and restore myelination to the denuded axons.
The experimental ground work has been laid for an attempt to treat spinal cord injury in humans with NSCs. The exciting news is the establishment of the worlds first clinical trial in spinal cord injured humans, including those with chronic injury is now underway in Switzerland. The trial is described below in the accompanying press release.
Press Release: GlobeNewswire Sep 22, 2011
StemCells, Inc. Announces World's First Neural Stem Cell Transplant in Spinal Cord Injury Patient |
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StemCells, Inc. (Nasdaq:STEM) announced today that the first patient in the Company's breakthrough Phase I/II clinical trial in chronic spinal cord injury was successfully transplanted with the Company's proprietary HuCNS-SC(R) adult neural stem cells. The stem cells were administered yesterday at Balgrist University Hospital, University of Zurich, a world leading medical center for spinal cord injury and rehabilitation. The transplant surgery was performed by a team of surgeons led by Dr. Raphael Guzman, a visiting staff neurosurgeon also on faculty at Department of Neurosurgery, Stanford University, and Dr. K. Min, an orthopedic surgeon at Balgrist University Hospital.
"I am pleased to be a part of this innovative clinical trial designed to help us assess the safety and potential efficacy of HuCNS-SC stem cells for spinal cord injury," explains Dr. Armin Curt, Principal Investigator. "The preclinical data underlying this trial provided compelling rationale to conduct a study of this nature in spinal cord-injured patients." StemCells, Inc. has published numerous preclinical studies demonstrating the therapeutic potential of the Company's human neural stem cells for the treatment of acute and chronic spinal cord injury. These studies were conducted in close collaboration with Drs. Aileen Anderson and Brian Cummings of the University of California, Irvine.
The first patient transplanted in the trial, a 23-year-old German man, suffered a spinal cord injury in an automobile accident in April of this year. He sustained a complete loss of sensation and mobility from the waist down. When asked about his decision to enroll in this leading-edge study, he said: "This terrible injury crossed out almost all my life plans, and has led me to an unexpected path. Participating in this clinical trial not only gives me a sense of hope, but it also helps move this important research forward."
"With this first patient enrolled and dosed, we remain on track to meet our goal of treating the first cohort of patients by the end of this year," said Stephen Huhn MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, Inc. "While the trial's first cohort will consist of patients with the most severe, complete injury, the second and third cohorts will progress to patients with less severe, incomplete injury. This unique trial design will allow us to evaluate the potential of our HuCNS-SC cells as a treatment for a broad spectrum of spinal cord injury patients. Even a small improvement could have a marked impact on quality of life for the millions of people who suffer from this debilitating condition."
About the Clinical Trial
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. Twelve patients with thoracic (chest-level) neurological injuries at the T2-T11 level are planned for enrollment. The first three patients will all have injuries classified as ASIA A, in which there is no apparent neurological function below the injury level, the most severe level identified by the American Spinal Injury Association (ASIA) Impairment Scale. The second and third cohorts will be patients classified as ASIA B and ASIA C, those with less severe injury, in which there is some preservation of sensory or motor function. In addition to assessing safety, the trial will assess preliminary efficacy based on defined clinical endpoints, such as changes in sensation, motor and bowel/bladder function.
All patients will receive HuCNS-SC cells through direct transplantation into the spinal cord and will be temporarily immunosuppressed. Patients will be evaluated regularly in the post-transplant period in order to monitor and assess the safety of the HuCNS-SC cells, the surgery and the immunosuppression, as well as to measure any recovery of neurological function below the injury site. The Company intends to follow the effects of this therapy long-term, and a separate 4-year observational study will be initiated at the conclusion of this trial.
For information on patient enrollment, interested parties may contact the study nurse either by phone at +41 44 386 39 01, or by email at stemcells.pz@balgrist.ch.
Additional information about the Company's spinal cord injury program can be found on the StemCells, Inc. website at http://www.stemcellsinc.com/Therapeutic-Programs/Clinical-Trials.htm and at http://www.stemcellsinc.com/Therapeutic-Programs/Spinal-Cord-Injury.htm, including video interviews with Company executives and independent collaborators.
About Chronic Spinal Cord Injury
According to a study reported by the Christopher and Dana Reeve Foundation, nearly 1.3 million people in the United States are estimated to be living with chronic spinal cord injury. The chronic phase of spinal cord injury is considered to begin when inflammation has stabilized and recovery has reached a plateau, which is typically several months following injury. Currently, there are no effective treatment options for patients with chronic spinal cord injury, and treatment approaches have generally targeted the acute and sub-acute time points, which are within hours or days of injury. Given the unmet need in chronic spinal cord injury, restoring some degree of function for patients at time points beyond the acute phase could have a transformative impact on the field. StemCells hopes to address a broad population of spinal cord-injured patients by opening the window of opportunity for therapeutic intervention well after the acute injury and targeting a wide range of injury levels and degrees of impairment.
About Balgrist University Hospital
Balgrist University Hospital, University of Zurich is recognized worldwide as a highly specialized center of excellence providing examination, treatment 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. More information about Balgrist University Hospital is available at www.balgrist.ch.
About StemCells, Inc.
StemCells, Inc. is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The Company's lead therapeutic product candidate, HuCNS-SC(R) cells (purified human neural stem cells), is currently in development as a potential treatment for a broad range of central nervous system disorders. Clinical trials are currently underway in spinal cord injury and in Pelizaeus-Merzbacher disease (PMD), a fatal myelination disorder in children. In addition, the Company plans to file an IND by year-end 2011 to initiate a clinical trial of HuCNS-SC cells in the dry form of age-related macular degeneration, and is also pursuing preclinical studies of its HuCNS-SC cells in Alzheimer's disease and stroke. StemCells also markets stem cell research products including media and reagents, under the SC Proven(R) brand, and is developing stem cell-based assay platforms for use in pharmaceutical research, drug discovery and drug development. Further information about StemCells is available at http://www.stemcellsinc.com.
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