Spinal Cord Injury (SCI) afflicts more than 300,000 Americans with staggering physical, emotional, and financial costs. Regenerative therapies for SCI do not exist. In this project, we have advanced the translation of a neural stem cell (NSC) program toward clinical development. We use human NSCs, derived from a federally-approved line of stem cells, to fill sites of SCI. Many of the grafted NSCs become neurons and send axons long distances into the host spinal cord. In addition, host axons regenerate a short distance into the graft. Together, the two phenomena create neuronal relay circuits, which can transmit information from the brain, across the injury site, to the spinal cord beyond. This program has met critical milestones of:  1) NSC survival and fill of sites of severe SCI; 2) functional improvement of the forelimb after cervical SCI and the hindlimb after thoracic SCI; 3) technology transfer to the non-human primate, with functional improvement; and 4) identification of the lead NSC for translational development. Most recently, the program has made detailed examinations of the candidate cell lines to ensure their safety and efficacy. The candidate cells are karyotypically normal, do not express cancer-related mutations, and have successfully differentiated past the embryonic stem cell stage. When grafted into rats for 3 months, the candidate cells did not form teratomas, or cause detrimental effects.

This program is now continuing as a CIRM TRAN award, intended to generate a NSC cell line using FDA-approved methods and to confirm these cells are safe and effective for transplantation into sites of SCI. Specifically, we will create Master and Working cell banks, develop release assays, lock-in a GMP-compatible protocol for large-scale production, extend ongoing safety and efficacy studies, and hold a pre-IND meeting with the FDA. We hope to transfer this promising technology to humans as a result of this support.