Thomas Burris, Ph.D., associate chair and professor in the University of Florida College of Pharmacy’s Department of Cellular and Systems Pharmacology and director of the UF Genetics Institute, has received a five-year, $3 million grant from the National Institutes of Health, or NIH, to pursue a new and safer approach to relief from chronic inflammatory pain.
Affecting at least 20 million Americans each year, chronic inflammatory pain, or CIP, is a debilitating condition in which pain is created by immune and inflammatory processes. Often the result of persistent tissue injury, recurrent inflammation or autoimmune and other chronic inflammatory disorders, CIP creates an annual burden of about $100 billion in lost worker productivity and healthcare costs. Burris said the NIH award allows his team to further the development of potential solutions — activators of biological targets known as REV-ERBs, which they’ve been investigating for more than a decade.
“This is certainly a validation of our efforts to understand the potential of developing REV-ERB agonists for clinical use,” Burris said. “We developed the first REV-ERB agonists that could be used in animal models of disease in 2012 and have been assessing their potential utility for some time now. We have made considerable progress, and this support allows us to continue to be at the forefront of drug development.”
Current therapeutic options for CIP include nonsteroidal anti-inflammatory drugs like aspirin, corticosteroids for flare-ups and opioids, but issues like reduced efficacy and severe side effects like opioid dependence and abuse motivated Burris and his team to look for a safer solution. Enter REV-ERB agonists — small, synthetic molecules that can activate REV-ERB, which is a receptor that regulates gene expression. Burris’ research has shown, when a REV-ERB receptor is activated, it can suppress key inflammatory genes that lead to chronic pain.
“Synthetic REV-ERB agonists are very effective in suppressing a range of inflammatory signals that would reduce pain associated with chronic inflammation. They are likely much more effective than nonsteroidal anti-inflammatory drugs and have the advantage over biologic anti-inflammatory drugs in that they can be taken as a pill,” Burris said. “Interestingly, we have also shown that these compounds not only have no addictive properties, but they appear to inhibit the addictive activity of other drugs.”
Using medicinal chemistry approaches, Burris’ team will first optimize REV-ERB agonists and then conduct preclinical trials to determine their capacity to treat CIP. Burris said this research provides a beacon of hope for the 1-2% of the world’s adult population who suffer from the chronic condition.
“CIP leads to substantial mental health comorbidities, reduced work capacity and early retirement, making it a significant contributor to societal and health system strain. Improved therapeutics to treat CIP, such as REV-ERB agonists, could improve health outcomes and quality of life,” Burris said.