Strategies to Improve Chronic Nerve Regeneration and Target Reinnervation
Abstract
Objectives and Rationale: The proposed research in this application addresses one of the major health issues facing Warriors wounded in combat. Although peripheral nerves do have a capacity to regenerate, functional recovery from peripheral nerve injuries is very limited, resulting in long-term disability. The limited functional recovery is due to loss and degeneration of cells in the nerve called Schwann cells that normally support the regeneration of nerves and atrophy and degeneration of the muscle. The molecular mechanisms that underlie limited functional recovery with proximal and chronic nerve injuries are not well understood, but our laboratory recently identified a key molecule that may prevent degeneration and loss of the Schwann cells (nerve support cells). It is called Glial maturation factor beta (GMF-ß). Combining this observation with previously published work demonstrating that another growth factor, insulin-like growth factor 1 (IGF-1), is able to prevent muscle atrophy when nerve input is lost, we hope to improve functional recovery after nerve injuries. Applicability of the Research: In this proposal, we will combine our expertise in drug delivery and nerve regeneration to achieve sustained release of these two growth factors delivered to injured nerve and muscle to prevent the degeneration and loss of Schwann cells and muscle cells. We will first encapsulate GMF-ß and IGF-1 in nanoparticles suitable for injection and sustained slow delivery and optimize their release kinetics. Then we will use a chronic nerve regeneration model in rats that mimic the slow nerve regeneration seen in humans and ask if we attain better functional recovery with this combined approach. We will accomplish these studies within 2 years of the proposal. If successful, the next step would be further preclinical development of the approach evaluating its safety and validation in additional large animal models of nerve regeneration prior to potential clinical trials. Military Benefit: Since many of the war injuries to extremities result in damage to the peripheral nerves, the proposed studies are directly relevant to war injuries sustained by Warriors. Furthermore, many civilians sustain peripheral nerve injuries through accidents. If the proposed studies show a significant benefit, then clinical development of nano-encapsulated GMF-ß and IGF-1 can be pursued for both military and civilian use.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710698
Entities
People
- Ahmet Höke
Organizations
- Johns Hopkins University
- United States Army