Dr. Steven Smith leads National Institutes of Health-funded study to determine minocycline’s potential to address treatment-resistant hypertension

By Tyler Francischine

Steven Smith, Pharm.D., M.P.H., FCCP, FAHA, interim chair of the University of Florida College of Pharmacy department of pharmaceutical outcomes and policy and co-director of the UF Center for Integrative Cardiovascular and Metabolic Disease, was recently awarded $3.3 million by the National Institutes of Health to study the effects of minocycline on treatment-resistant hypertension, or TRH, a condition affecting as many as 200 million people globally that’s defined as requiring at least four antihypertensive drugs to achieve blood pressure control.

Smith says the link between minocycline, an older and rarely prescribed antibiotic, and TRH lies in the mechanisms underlying TRH: gut dysbiosis and neuroinflammation.

“When gut dysbiosis occurs, there’s a depletion in the production of butyrate and other short chain fatty acids, an important energy source for many cells and important organs that control blood pressure,” Smith said. “We also know that TRH is highly associated with inflammation and disruptions in the sympathetic nervous system. We think gut dysbiosis creates metabolites or other byproducts that cause the immune system to ramp up, especially in the brain. That immune system response leads to sustained elevations in blood pressure that persist despite use of antihypertensive drugs.”

Smith’s team will spend the next five years conducting a randomized clinical trial of minocycline versus placebo to determine the extent that these mechanisms contribute to the blood pressure-lowering effect of minocycline, and whether these mechanisms may differ in Black and white Americans. With TRH’s increased risks of heart attack, stroke and death, Smith’s research stands to leave a lasting impact on this large patient population.

“As an antibiotic, minocycline has an effect on the microbial communities of the gastrointestinal tract, and it also has anti-inflammatory effects on the brain. If the research shows that minocycline lowers blood pressure in these individuals, it opens the door for a new opportunity to better understand these mechanisms, with the ultimate goal of drug development that targets the mechanisms causing TRH,” Smith said. “It’s very exciting to have the NIH recognize these opportunities.”

Smith said this project exemplifies the collaborative, translational work being done each day at the UF Center for Integrative Cardiovascular and Metabolic Disease, a center whose team is committed to advancing UF’s cardiovascular and cardiometabolic research.

“One of the main goals of the center is to cross disciplines and break down these silos between basic science and clinical science researchers. With this work, we’ve demonstrated that we can take ideas that originated in the basic science labs and see them through to interesting — and potentially practice-changing — clinical science projects,” Smith said. “I’m really proud of that, and I’m hopeful that the center can continue to foster these types of projects.”