Final-Stage Preclinical Development of a Long-Acting, Non-Opioid Peptidomimetic Drug for Chronic Pain
Abstract
The lack of effective treatments for chronic pain has led physicians to prescribe opioids. This has led to an opioid epidemic. From 2010 to 2019, opioid overdose deaths climbed from 21,088 to 49,860, with dependence in one out of four patients receiving opioids prescriptions. There is, therefore, an urgent need to develop new non-addictive drugs to prevent and treat chronic pain. A key protein responsible for the development and maintenance of chronic pain is the repressor element-1 (RE1)-silencing transcription factor (REST). Therapeutically targeting REST has not been feasible because of technical challenges associated with drugging transcription factors (e.g., the lack of small molecule binding pockets and nuclear localization, which makes them inaccessible to antibodies). Using our proprietary protein engineering technology, we have developed a potent and selective peptidomimetic drug that inhibits the enzyme that controls REST activity (CTDSP1). Our drug has a stable structure and is cell permeable, allowing for a convenient dosing regimen (>/= daily) and route of administration (topical or subcutaneous). With this proposal, we aim at completing the nonclinical package required by the U.S. Food and Drug Administration (FDA) to start first-in-human studies. The proposed research addresses the FY21 PRMRP topic area of Non-Opioid Therapy for Pain Management and the area of encouragement: Development of non-opioid non-addictive pain management therapies, including non-pharmacological interventions and those that do not affect the cardiorespiratory system. Specifically, the proposed project aims to develop a novel, long-acting, non-opioid drug to both prevent the molecular changes responsible for the conversion from acute to chronic pain and to treat chronic pain once it has developed.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210385
Entities
People
- Leon Nesti
Organizations
- United States Army