AI Derived Therapeutic Development for the Treatment of Opioid Use Disorder

Abstract

The opioid epidemic has led to a devastating loss of life nationwide. Of those dependent on opioids, many individuals desire to quit or reduce use, but their efforts are often unsuccessful given the powerful reinforcing properties associated with opioid drugs, especially fentanyl given its high potency and speed of onset. Here, we developed a novel theraputic based on a newly developed artificial intelligence (AI)-based platform, which was rationally designed to identify markers of dysregulation from human drug user postmortem brain tissue. The GATC-021 compound was synthesized and validated with in vitro screening for target specificity. Thereafter, GATC-021 was examined for its effectiveness in modulating opioid dependence with an animal model of addiction. We found that GATC-021 substantially reduced fentanyl intake in both male and female rats, as assessed with intravenous self-administration. However, given drug soluability challenges, additional studies are needed to better develop drug formulations to permit translation into clinical populations more effectively. Taken together, these findings validate our AI-based platform for novel therapeutic development with a polypharmacy approach and further support the effectiveness of such target modulation as a promising therapeutic approach for those suffering from opioid use disorder.