Grant Award Details
Neural Stem Cell Relays for Severe Spinal Cord Injury
Spinal Cord Injury
<p>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.</p><p>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.</p><p> </p>
Grant Application Details
- Neural Stem Cell Relays for Severe Spinal Cord Injury
We propose to utilize human neural stem cells to form neuronal relays across sites of severe SCI, restoring function across the site of spinal cord injury.
We will develop a specific type of neural stem cell that is best suited for repairing the injured spinal cord.
Major Proposed Activities
- In Vitro Assessment of GMP-compatible H9-scNSC Batches.
- In Vivo Assessment of GMP-compatible H9-scNSC Batches.
- In Vivo Assessment of Disease Modifying Activity over time, Model 1: T10 moderate contusion.
- In Vivo Assessment of Disease Modifying Activity over time, Model 2: T3 severe compression.
- In Vivo Assessment of Disease Modifying Activity over time, Model 1: C5 moderate contusion.
- FDA Pre-pre IND Meeting.
Statement of Benefit to California:
Spinal cord injury (SCI) affects approximately 300,000 people in the U.S., with more than 11,000 new injuries per year. This research plan will examine a novel therapeutic strategy for SCI. Neural stem cells will be generated from human embryonic stem cells and grafted into animal models of SCI. We predict neuronal relays will form across a SCI lesion site that will mediate behavioral recovery. These studies will form the basis for clinical translation for the treatment of spinal cord injury.
Source URL: https://www.cirm.ca.gov/our-progress/awards/neural-stem-cell-relays-severe-spinal-cord-injury