Mitochondrial Transplantation Combined with Mitochondrial-Targeted Pharmaceuticals to Treat Spinal Cord Injury
Abstract
Traumatic spinal cord injury (SCI) is an unresolved long-term health care problem in the United States, which has initiated an enormous focus on the development and discovery of neuroprotective and/or pro-regenerative drugs, which might have clinical relevance after injury. However, there are currently no clinical pharmacological treatments approved for this devastating condition. Using animal models of experimental SCI, we have shown that mitochondrial organelle dysfunction plays a pivotal role in development of secondary injury cascades that further neuronal damage, ultimately resulting in chronic paralysis. Therefore, the proposed experiments are designed to test the protective efficacy of drugs we have reported to target and promote mitochondria to maintain the health of host spinal cord cells, both alone and in combination with novel mitochondrial transplantation (MitoTxp) techniques into the spinal cord for long-term functional recovery following contusion SCI. We also propose to use minimally invasive subdural delivery of mitochondria over the injury site using specialized polymer hydrogels that enable localized diffusion of healthy mitochondria, which we have found can diffuse into spinal cord tissues. Since we have found that mitochondrial drugs can be delivered effectively within hours after SCI, we anticipate that MitoTxp can take place within hours to a day later to promote greater functional recovery. With the refinements made to more broadly deliver mitochondria to the site of injury, there is strong potential to move this acute therapeutic strategy closer toward clinical trials for early management of traumatic SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010347
Entities
People
- Alexander Rabchevsky
Organizations
- United States Army
- University of Kentucky