Spinal cord injuries (SCI) in the US affect 10-12,000 new individuals each year, with a chronic population of 250,000. In addition to the human suffering, lifetime costs exceed $2.9 million for cervical SCI, not including lost wages and productivity. Since SCI is a focal CNS lesion, cellular replacement with stem cells is a logical approach to therapy. We propose to initiate a disease team planning process in order to prepare for the submission of a disease team proposal that will seek CIRM funding for preparing stem and progenitor cell based therapies for clinical use in SCI. The planning team will include SCI researchers and stem cell biologists from throughout the state of California. Expert consultants will be brought in to help lead workshops aimed at clearly defining the targets and strategies for stem cell based therapies for SCI. Specialized cells derived from glial progenitor cells have been effective in a number of laboratory studies of spinal cord repair, and these will be the focus of the planning process. Several types of glial progenitors derived from human fetal or embryonic stem cells will be candidates for intensive preclinical studies that will be designed during the planning process. These will be honed to 3 or 4 possibilities, with definitive criteria for phenotyping, and the process for obtaining cell population purity. These criteria will be included in the disease team proposal. Current gaps and roadblocks will be determined during the planning process, starting with in depth discussions of the following issues: 1. Can cell based therapies be used in chronic as well as acute SCI? The chronic SCI population is actually more suited to clinical trails, but data from the lab suggests that chronic SCI may be less amenable to treatment with stem cells. 2. What are the immunological challenges of non-self vs autologous transplantations? 3. Which cell types are most promising for therapies? and 4. what are the roadblocks to bringing them into production for clinical trails? 5. What methods can be used to control the hostile tissue microenvironment of the injured CNS? Anti-inflammatory and bioengineering approaches will be examined. 6. Should we use large animal models as an advanced test for safety and efficacy? 7. Seeing ahead to the clinical application process will require much advanced planning and the incorporation of GMP and GLP. The PI is a seasoned research team leader with years of experience in developing preclinical SCI models in rodents and is funded by NIH to develop cell-based transplantation therapies in these models. The Co-PI is an eminent, NIH-funded M.D./Ph.D. neurosurgeon with basic science, clinical trials and therapeutic development experience in neurotrauma. The combination of two highly collaborative “leaders among equals” with experience in preclinical and clinical neurotrauma research and practice will provide a critical synergy between the scientific and clinical aspects of the planning process.
Statement of Benefit to California:
Spinal cord injuries (SCI) in the US affect 10-12,000 new individuals each year, with a chronic population of 250,000. In addition to the human suffering, lifetime costs exceed $2.9 million for cervical SCI, not including lost wages and productivity. This planning grant will bring together researchers and clinicians dedicated to helping solve the enigma of SCI and paralysis, leading to increased cooperation in the search for therapies that will improve outcomes. The work done in the subsequent disease team project will help move stem cell based therapies into preclinical and clinical trials. If these are successful, every resident of the state of California who has, or knows someone with an SCI is a possible beneficiary. In addition, the therapies developed for SCI using glial cells are likely to be applicable to other disorders of the nervous system, including traumatic brain injury, multiple sclerosis and other white matter disorders such as infant brain damage. The technology generated by this work is also likely to pay economic dividends to the state and its residents and companies through new patents and licensing agreements.