Targeting Serotonergic Receptors to Treat Spinal Cord Injury
Abstract
Significant efforts have been made in the development of new treatments for spinal cord injury (SCI), from basic science research through clinical application. However, the far more challenging goal of restoring bladder function to improve the quality of life among SCI patients has still been largely underachieved. The spinal cord segments below the injured level undergo remodeling to adapt to changes in spinal circuits that control lower urinary tract (LUT) function (bladder and external urethral sphincter). Particularly, the 5-HT (a neurotransmitter released form the nerve fibers) and 5-HT receptors have been shown to play important roles in regulating LUT function in both normal and SCI conditions. To develop a clinically applicable therapeutic to improve LUT dysfunctions caused by SCI, we first will use comprehensive approaches with pharmacological interventions to activate 5-HT receptors to determine their efficacy on improving LUT function in a clinically-relevant contusive SCI model. Importantly, our recent study showed that long-term activation of 5-HT<1A> receptors (a subtype of 5-HT receptors) by a promising compound called NLX-112 can improve LUT function after contusive SCI. NLX- 112 is a drug that is currently in a phase 2 clinical trial to treat Parkinson’s disorders. We will further compare the pharmacological efficacy on improving LUT function between NLX-112 and the current clinically available compounds, and study the potential mechanisms underlying NLX-112 improvement of LUT function after SCI. Therefore, success in this project will move NLX-112 forward toward clinical application in SCI patients to address LUT dysfunctions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310412
Entities
People
- Yu-shang Lee
Organizations
- Cleveland Clinic
- United States Army