The search for a better overdose reversal agent

The Jackson Laboratory's Jason Bubier. Photo credit: Tiffany Laufer The Jackson Laboratory's Jason Bubier. Photo credit: Tiffany Laufer

The search for a better overdose reversal agent

Fatal opioid drug overdose deaths are rising steeply both in Maine and nationwide, exceeding 600 and 100,000 respectively in 2021. Unfortunately, the spread of ultrapotent synthetic opioids (UPS) such as fentanyl and even more dangerous forms, including nitazenes, is likely to continue the trend. Of additional concern is that the current opioid response agent, Naloxone, is not as effective against UPS, necessitating the development of a new, more powerful reversal agent.

Jackson Laboratory (JAX) Senior Research Scientist Jason Bubier, Ph.D., investigates the biological bases of drug addiction and risk for opioid overdose. Now, supported by a three-year, 1.3M grant from the National Institute on Drug Abuse, Bubier will lead research to determine the molecular mechanisms underlying individual variability to fentanyl toxicity using genetically diverse mice. One part of the study will focus on a gene, Mcoln1, identified in a genome-wide association study of overdose risk, to see how it affects response to fentanyl and how other genes and variants might modify its influence. He will also investigate fentanyl response across eight genetically diverse inbred mouse strains and how differences in gene expression contributes to variable responses. The insights gained will help identify targets for therapeutic development.

Learn more about Bubier’s research into opioid-induced respiratory depression:

Bubier also delves into other aspects of the biology of addiction: