“Neural Stem Cells for Spinal Cord Injury: Studies leading to an IND”

We propose to advance a clinical program of neural stem cell therapy for spinal cord injury (SCI) to an IND submission and clinical trial. Our work to date has demonstrated that Neural Progenitor Cells (NPCs) and Neural Stem Cells (NSCs) survive grafting to the spinal cord and extend very large numbers of axons over long distances through the lesioned rodent and large animal spinal cord. Host axons also regenerate into cell grafts occupying the lesion site, and form new synaptic connections that act as neural relays across the injury to support functional improvement in both rodents and large animals. We have identified a lead candidate human NSC/NPC line for clinical translation: an H9 human embryonic stem cell (a federally approved human cell line) that is driven to a spinal cord NSC/NPC fate. We refer to these cells as H9-scNSCs. H9-scNSCs survive grafting to cervical spinal cord hemisection and contusion lesions. This promising line of work is advancing on a translational path, supported extensively by the VA’s RR&D Gordon Mansfield Spinal Cord Injury Consortium. We aim to bring this work to the point of readiness for human clinical trials in SCI. The goal of the current application is to advance this program to submission of an FDA IND, with the eventual goal of a human clinical trial of this promising approach. For the 4 year funding period, this project will support characterization of cells, assay development, IND-enabling in vivo studies, project management and the services of regulatory experts with experience in FDA submissions.