Pursuing Safer Pain Relief Without Addiction

Professor Jeff Aubé and a team of collaborators seek to end the opioid crisis at the source

Story by Ryan McDaniel | Photo credit Jenna Miller | Published May 23, 2023

Jeff Aube headshot, taken outside

In 2009, at the University of Kansas, Jeff Aubé, PhD sat in a faculty meeting doodling. In his hands, this idle distraction took the form of chemical structures and, soon, a reaction sequence. Recognizing he had something intriguing in his hands, Jeff brought the doodles back to his lab. “Basically, we started working on that,” he recalls. “Not with any particular therapeutic goal in mind or anything – it was just an interesting set of molecular structures.”

His lab sent the molecules to various biologists for screening, including the Psychoactive Drug Screening Program at UNC. The screens revealed that some of these compounds are very potent kappa opioid receptor (KOR) acting agents. This holds great potential as an alternative analgesic to the most common opioids, which target the delta and mu receptors as well as KOR. “Morphine, for example, is a global agonist, meaning it interacts with all of the opioid receptors,” Jeff explains. “What we’re doing here is slicing away two and just focusing on the one – the kappa receptor.”

This work could bring about drugs that treat pain without the addictive properties of today’s opioids – an innovation that would be a major step in curtailing the opioid crisis. The NIH reported over 80,000 opioid overdose deaths in 2021, highlighting the urgent need for research like this. “Our goal is ultimately to come up with agents that function in a fundamentally different way than those existing drugs,” Jeff explains. “It’s a very ambitious long-term goal, and I want to be very cautious about making anybody think we’re going to have a drug coming out next year.”

The work is moving along, though, and compounds are in pre-clinical development, about mid-way through the pipeline of new drug creation. Jeff, now an Eshelman Distinguished Professor at the UNC Eshelman School of Pharmacy, has found that animal models suggest these compounds activate the KOR without the typical debilitating side effects arising from most KOR agonists. His lab is working to translate that into human medicine. It is a challenge, but Jeff remains optimistic. “It’s actually been part of the charm of working in science for me,” he notes. “Because I’ve always had a feeling of contributing to this stream of innovation and work that started before I was born and will continue long after I’m gone. It’s been a very gratifying aspect of being in this line of work.”

Laura Bohn, PhD, Professor and Chair of Molecular Medicine at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology has collaborated with Jeff on this work for over a decade and also notes the promise of this approach. “Jeff has been prolific in generating novel chemical probes that are highly selective for the kappa opioid receptor,” she notes. “Together, we have been working to refine KOR therapeutics and have discovered drug candidates that have the useful properties such as analgesics or anxiolytics without the side effects.”

The American Association of Colleges of Pharmacy (AACP) has taken note of the great work Jeff and his collaborators have been doing in this and other areas. Jeff recently received the prestigious Volwiler Research Achievement Award. “It recognizes not just me, but all these amazing people I’ve worked with over the years,” Jeff says of the honor. “I’m grateful that I have had the chance to work with all of them. I’m glad the collaborative work we’ve done is recognized and appreciated.”

That recognition and appreciation also acts as further motivation for Jeff and the team of collaborators. While the development of these compounds into viable drugs is a complex and ongoing process, these researchers remain dedicated to advancing pharmacology and improving the lives of countless individuals, working toward a future where pain relief is attainable without the devastating consequences of addiction.

This story highlights just one of the School’s initiatives to combat the opioid crisis. Read about other initiatives here:
Combating the Opioid Crisis from the Inside Out
First In Venture Studio Takes Aim at the Opioid Crisis