Spinal cord injury is a particularly debilitating form of trauma, in part because there is no current curative treatment. The unmet medical need in patients who have suffered paraplegia or quadriplegia has long been recognized as one that is in need of novel therapeutic approaches. Stem cell-based strategies may offer a broad regenerative platform that may address many aspects of the injury to the spinal cord and create opportunities to intervene long after the initial trauma. Spinal cord injury (SCI) affects a variety of neural cells, such as neurons and oligodendrocytes. The latter produce myelin, an insulating sheath that ensures normal conductivity. Therefore, an approach that offers the replacement and/or restoration of function to damaged cells holds much promise. Research has now shown that cell therapy may be capable of producing more than one effect in the injured spinal cord. The spectrum of benefits derived from this approach explains why this area is now a major research focus not only for SCI, but other neurological diseases as well.
Research with central nervous system stem cells derived from the human brain have demonstrated that these cells survive after transplantation, differentiate into neurons and oligodendrocytes, and most importantly improve neurological function in animal models of SCI. One of the first steps prior to testing a potential therapy in humans is to conduct animal experiments in models that reflect the human trauma as closely as possible. Therefore the primary goal of this research is to establish further evidence that the human central nervous system stem cell (HuCNS-SC) is safe when transplanted into the spinal cord, and that it also leads to a better recovery when compared to animals that did not receive transplantation. The research proposed will study the effects of HuCNS-SC cells in the setting of lower SCI (thoracic cord trauma that results in paraplegia) and upper SCI (cervical cord trauma that leads to quadriplegia) in animal models that will allow survival of the human cells. Effectiveness will be tested by measuring neurological function and determining the degree of improvement after transplantation of the human cells. Safety will be tested by closely examining the animals to show that there are no adverse reactions to the transplanted cells.
Investigating the effects of human central nervous system stem cells in these animal experiments will enable collection of data necessary to begin human clinical trials. The regenerative therapy potential represented by stem cells for patients with spinal cord injury has captured the imagination of scientists and patients alike. The opportunity to embark on this exciting field of research shows that new approaches are on the horizon and the field of cell therapy for spinal cord injury will be significantly advanced by the results obtained in this research program.
Statement of Benefit to California:
Spinal cord injury (SCI) causes a devastating condition; its effects vary depending on the level and degree of damage to the spinal cord. The trauma usually occurs at younger ages and results in a lifetime of paralysis which becomes associated with other medical complications and creates significant demands on the health care system. SCI is the second leading cause of paralysis in the US and it is currently estimated that there are approximately 1.3 million affected individuals. Although there are no official estimates, it is projected that there are more than 140,000 Californians living with SCI. In addition to the considerable personal burden placed on the individual and family, the economic impact of SCI is highly significant. The estimated costs related to loss of wages and health care for affected patients may be higher than 1.5 billion dollars annually for patients living in California. A therapy that can restore at least some spinal cord function has the potential for a significant improvement not only in the patient’s quality-of-life, but also the shared costs of health care and loss of productive employment.
The use of stem cells, and in particular human central nervous system stem cells (HuCNS-SC) , as therapeutics for SCI holds much promise for ailing patients. Most clinical investigations for SCI have focused on developing treatments that are aimed at very early time points after injury and have not been associated with major changes in outcome. This research will focus on developing an approach that will have broader applicability in terms of larger window of treatment after injury and include both upper and lower levels of spinal cord trauma. The development of a novel treatment that can address time points beyond the acute phase of trauma, and include thoracic as well as cervical levels, will more fully address the unmet medical need of the entire spectrum of patients with SCI. The range of potential benefit to patients includes improved sensory, motor, bowel/bladder, and even important reflex, or autonomic, function. A change in any one or combination of these deficits, if only for one or two spinal cord functional levels, could translate into improved quality-of-life for a patient.
The results of the research proposed will enable the regulatory approval and execution of clinical trials using hCNS-SCns to treat spinal cord injured patients. This research program will capitalize on the combination of a team of world-class scientists and clinicians in California that together can advance this field of endeavor. The outcome of the proposed studies will help not only those Californians with SCI, but will more globally pave the way for the use of stem cells in a variety of diseases. Additionally, our California-based effort will not only help individuals ailed by this state, but will also ensure that California ranks very highly in terms of SCI therapeutic advances and benefits from jobs created and retained.