Topical Hedgehog modulators to enhance motor nerve regeneration after injury and repair

Abstract

To improve peripheral nerve regeneration after injury, we will test three methods of modulating a critical molecular pathway using topical application of powerful pathway agonists applied to sites of surgical nerve repair. Our compelling preliminary and published data show that systemic administration of our small molecule prior to nerve transection injury improves nerve regeneration and functional recovery after injury. To limit the risk of systemic toxicity, we propose translating these findings to a topical pathway modulator applied directly to the nerve during surgery. This proposal capitalizes on our unique knowledge of nerve repair surgery to create a feasible method to administer targeted biological modulators during these procedures.