Grant: Project Grant

Spinal cord injury (SCI) is a leading cause of permanent neurological disabilities affecting over 2.5 million individuals worldwide. In Canada, there are over 86,000 patients who are afflicted with lifelong consequences of SCI with approximately 4,200 new cases each year. The lifetime medical cost of each SCI patient is estimated at 1.6 to 3 million dollars. Thus, SCI has a profound impact on patients, their caregivers, and the healthcare system. Currently, there is no effective treatment for SCI and new therapies are needed to allow neurological improvement in patients. Extensive research by our group and others show that transplantation of neural stem cells offers tremendous possibility for SCI repair. Indeed, based on these experimental discoveries, neural stem cell transplantation has moved to clinical trials in recent years. Initial outcomes of these trials indicate that while neural stem cells are safe and promising for treatment of SCI, their benefit for neurological recovery of patients is only modest. We have made the same observation in our experimental evaluations, establishing a need for combinatorial therapies to augment the functional outcomes of current cellular therapies. To this end, we have discovered new therapeutic targets with the potential to harness the regenerative capacity of neural stem cells for repairing the injured spinal cord. We have identified that formation of a glia scar around the lesion and increased production of inhibitory molecules in the scar limit the benefits of neural stem cell transplantation. We show that inhibiting these factors facilitates the longterm survival of stem cells and their abilities for tissue regeneration. We are currently investigating several aspects of these strategies and importantly their potential in improving functional recovery in an animal model that clinically reflects human SCI. Our goal is to develop effective regenerative medicine strategies for improving the quality of life in SCI patients.