Funded Projects

Chronic pain affects an estimated 100 million Americans, or one third of the U.S. population, and it is the primary reason Americans are on disability. Although many treatments are available for pain, the most potent class of analgesics relies on opioid analogs, whose limitations and well-known adverse effects have contributed to the present opioid crisis. New pharmacotherapies for pain management are sorely needed. MTX1604, a synthetic endomorphin analog, has emerged as a highly effective analgesic that exhibits reduced reward potential and respiratory suppression, and a robust duration of efficacy in a variety of validated animal models of acute, neuropathic, inflammatory, post-operative, and visceral pain. This project will generate additional preclinical characterization data of MTX1604 and advance clinical development toward FDA approval. If successful, this medication development project could offer patients a novel non-addictive, potent, and safe analgesic and thus have a direct impact on the opioid crisis.

Over 2 million Americans have an Opioid Use Disorder (OUD) and the risks associated with misuse of opioids have prompted a public health crisis. There are three effective FDA-approved drugs for medication assisted treatment (MAT) of OUD. However, while MAT can reduce overall OUD related mortality by as much as fifty percent, relapse and treatment discontinuation are common within the first 5 to 12 weeks of MAT. As longer treatment retention is correlated with better long-term outcomes, the development of an adjunctive medication to alleviate key psychiatric symptoms associated with treatment failure would address an important unmet need. This study seeks to evaluate the safety and efficacy of brexpiprazole as adjunctive treatment to buprenorphine/naloxone in OUD. If successful, this study could enhance the effectiveness of OUD treatments by extending the duration of treatment, thereby reducing the likelihood for relapse and overdose.

Fentanyl and its analogs are synthetic opioids that are 100 to 10,000 times more potent than morphine. Overdose from these opioids is extremely dangerous due to their ultra-potency and longer half-life than naloxone, the front-line treatment for fentanyl overdose. This research study will develop novel mu opioid receptor antagonists that bind to the same receptor as the opioid drugs and specifically counteract fentanyl and its analogs, thereby reversing the drugs’ acute toxicity more effectively and with fewer side effects than current treatments. The researchers will characterize novel fentanyl derivatives, identify promising compounds, and pursue preclinical development of these compounds as novel reversal agents against the acute toxicity of fentanyl. The goal is to file an Investigational New Drug application with the U.S. Food and Drug Administration.

This project aims to develop a new way to stimulate the delta opioid receptor to treat withdrawal and abstinence from chronic opioid use. Withdrawal can cause pain, depression, and anxiety, which contribute to relapse. The research will test promising drug candidates in animal models with the intention of bringing at least one effective and safe compound to the final stage of drug development before human clinical trials can begin.