Nonpeptide Neurotrophic Mechanisms in Spinal Cord Repair

Ashiwel Undieh | The City College of New York

Dr. Ashiwel Undieh, Professor of Neuroscience & Pharmacology

City University of New York School of Medicine

 

Dr. Ashiwel Undieh, Professor of Neuroscience & Pharmacology at the City University of New York School of Medicine was recently awarded a four-year, $628,000 grant (1R16NS1296751) from the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). The project is entitled Nonpeptide Neurotrophic Mechanisms in Spinal Cord Repair.

Severe spinal cord injury (SCI) remains incurable as there are no medications that can reverse the injury-related nerve tissue damage. “While neuroelectrical and exoskeletal strategies have recently produced promising improvements in motor deficits, the holy grail of SCI therapy is corticospinal nerve regeneration with functional neurorecovery. Our research strategy seeks to boost the actions of nerve growth factors or neurotrophins that are known to promote regeneration even in adult nerve tissues. We have identified several small-molecule compounds able to promote the regrowth of damaged nerve cells in a tissue culture model,” shared Dr. Undieh who also is head of the School’s Neuromedications Innovation Lab. This finding is particularly intriguing because these compounds are not proteins or peptides like natural nerve growth factors. “We will study and elucidate upon a novel mechanism of action shared by these nonpeptide neurotrophic compounds and subsequently apply the knowledge gained toward repurposing existing drugs or designing new compounds that promote nerve cell regrowth and repair damaged nerve connections to treat SCI patients.”

Previous funding from the New York State DOH Spinal Cord Injury Research program supported preliminary research that facilitated the present NIH award.

Project Abstract
Traumatic spinal cord injury (SCI) is associated with deficits in sensory and motor function, including complete paralysis in severe cases. Unlike peripheral tissues that can heal and regain function following lacerations and contusive injuries, the spinal cord is notoriously resistant to regrowth or replacement of neural connections with the brain after injury. The overall goal of this research is to increase understanding of neuroregenerative mechanisms and uncover novel pharmacological targets for the treatment of SCI. Experiments in animal models suggest that boosting the biological activity of nerve growth factors in the spinal cord can nudge the tissue toward a program of regeneration. Following rational selection and screening of several small-molecule compounds, we found several members to potently promote the regrowth of damaged nerve cells in a tissue culture model. Some of these compounds are being used as approved drugs for other disorders, and all six compounds are capable of crossing into the CNS from the bloodstream. The shared biochemical properties of the compounds leads to a hypothesis which links the actions of these nonpeptide neurotrophic compounds to the pathways of growth factor signaling and regenerative effects. The logical next step is to clarify the mechanism by which these compounds work. 
 

Last Updated: 07/07/2022 13:17