SCI Regeneration and Recovery via Tandem Cell Replacement and CSPG Inhibition
Abstract
This proposed project is directed at overcoming barriers to spinal cord injury (SCI) repair and to promote full functional recovery following SCI by combining two new approaches: the replacement of damaged neurons by stem cells via a novel bioengineered graft; and the promotion of plasticity and neuro-repair by the drug NVG-291, currently in commercial development by NervGen Pharma Corp. On the heels of excellent pre-clinical evidence of efficacy of NVG-291 in restoration of critical functions after SCI, NervGen has begun collaboration with the University of Akron (UA) through Nic D. Leipzig, PhD., PI. The aims of the research at UA are utilizing a combinatorial approach of engineered biomaterials, regenerative neural stem cells (NSCs), and NVG-291 to improve patient outcomes following SCI. NSCs differentiate into specialized cell types known as neurons and oligodendrocytes to repair neuronal damage. Newly formed neurons repair brain and spinal cord lesions, and oligodendrocytes promote axonal regeneration and remyelination. Following neuronal damage, chondroitin sulfate proteoglycans (CSPGs), a potent inhibitor of nervous system repair, increase and inhibit repair and regeneration. NVG-291 is a clinical-stage compound developed by NervGen based on research from Case Western Reserve University that modulates the cellular response to CSPGs after central nervous system (CNS) injury and promotes plasticity (the nervous system’s ability to change and adapt). In addition to the plasticity enhancing effects, previous animal studies in SCI and stroke show that NVG-291 treatment led to increased NSC migration and integration into the CNS and differentiation into neurons. NVG-291 can circumvent three challenges posed by NSC cell replacement therapies. Firstly, for effective treatment, NSCs must be administered via invasive delivery directly into the spinal cord, which can exacerbate the damage. NVG-291 enhances migration of the stem cells into the host tissue, reducing the need for multiple stem cell therapies. Secondly, the lesion promotes differentiation of NSCs to unfavorable astrocytes at the expense of oligodendrocytes and neurons. NVG-291 has been shown to reduce the generation of astrocytes and increase the generation of neurons and oligodendrocytes. Thirdly, integration of differentiated cells into the host tissue is challenging, and NVG-291 promotes new neural connections in all directions, creating a relay to bypass damage. NSCs and NVG-291 are individually promising therapeutic approaches to restore function following SCI. Research into combining these therapies is necessary to improve functional recovery to a much greater extent than either treatment alone, with NVG-291 optimizing the effects of NSCs and promoting neuro-repair.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310891
Entities
People
- Nic Leipzig
Organizations
- United States Army
- University of Akron