Interdisciplinary Initiatives Program Round 12 - 2024
Project Investigators:
Sarah Heilshorn, Materials Science & Engineering
Helen Blau, Microbiology & Immunology - Baxter Laboratory
Abstract:
Cervical spinal cord injury (SCI) is devastating, and there is currently no cure. To these patients and their caretakers even a modest functional recovery could lead to a substantial improvement in their quality of life, highlighting the critical need for new therapies for SCI. This proposed interdisciplinary collaboration combines expertise in materials science and cell biology to explore an intriguing hypothesis that manipulation of prostaglandin E2 (PGE2), a lipid metabolite that is part of the body’s natural healing mechanism, can protect spinal neurons following SCI and induce recovery of sensory and motor function. After cervical SCI, the combined impact of primary mechanical injury and subsequent biochemical secondary injury leads to the death of local spinal neuron populations and the formation of a cystic cavity. Limiting the spread of this neuronal death and cystic cavity has been shown to result in improved motor function in preclinical animal studies. Here, we hypothesize that sustained delivery of a drug that boosts PGE2 function by inhibiting its degradation will provide long-term protection to spinal neurons, prevent progression of secondary injury, and restore behavioral function. This pharmaceutical approach to neuroprotection was shown to be successful in a peripheral nerve injury model, but required daily drug injections for 30 days, which is not suitable for SCI therapy. To develop a clinically relevant therapy for the central nervous system, we propose the design and optimization of an injectable, biodegradable gel that provides local, sustained drug-release at the site of cervical SCI. The success of our study would identify new neuroprotective pathways in SCI, leading to the development of a novel therapy for SCI patients worldwide.
