Scope: Pilot Project-Park: COBRE in Pharmaceutical Research and Innovation

Traumatic primary spinal cord injury (SCI) impairs the quality of life for patients, with permanent loss of function below the injury. As a secondary injury, the excessive neuroinflammatory responses play a key role in functional deficits after SCI. The acute interventions targeting inflammation for SCI are promising, yet chronic SCI is more clinically relevant and may be even more challenging. Currently, therapeutic neuroprotective strategies mainly target locomotor recovery and very little attention has been devoted to understanding neuropathic pain even though up to 80% of SCI patients experience clinically significant neuropathic pain within months. In addition, many patients suffer from adverse effects of traditional pharmacologic treatments, such as opioid addiction. The scientific premise of this proposal is to establish highly translatable combinative multi-stage therapeutic strategies to treat SCI-derived locomotor and somatosensory dysfunctions simultaneously. Due to the complex nature of SCI, combinative multi-stage approaches will be employed to limit excessive inflammatory responses and create an environment to support regeneration. This proposal will focus on 1) employing acute gene delivery and nanotechnology to reprogram innate immune cells’ properties, 2) providing mechanical guidance cues via chronic biomaterial implantation to enhance robust axonal outgrowth and synaptic continuity into appropriate functional fascicles for regeneration, and 3) incorporating neuropathic pain-silencing factor with biomaterial to alleviate chronic sensory dysfunctions after SCI. Collectively, acute delivery of immunomodulatory factors will modulate an inhibitory environment and spare regeneration-competent axons, and that combination of this approach with delayed biomaterial implantation with neuropathic pain-silencing factor will lead to locomotor and somatosensory functional restorations in the chronic SCI.