Peters Awarded $418,000 to Continue Study on Repurposing Compounds to Fight Yeast Infection Inflammation

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Dr. Brian Peters (Photo by Connor Bran/UTHSC)

Brian M. Peters, PhD, assistant professor in the Department of Clinical Pharmacy and Translational Science in the College of Pharmacy at the University of Tennessee Health Science Center (UTHSC), has recently been awarded $418,000 to continue his research repurposing compounds to fight against inflammation that results from vulvovaginal candidiasis (VVC) — commonly referred to as a yeast infection. VVC is among the most prevalent fungal infections found in humans — 75 percent of women suffer from this condition at least once in their lifetime.

“Current therapies for VVC are focused mostly on antifungal administration, which for the most part, is fairly effective,” Dr. Peters said. “But there is a subset of women (five to eight percent) who have recurrent disease and have to maintain that antifungal therapy throughout their lives, or they will continue getting symptoms over and over again.”

Dr. Peters and his team are attempting to develop a potential new way to treat VVC by repurposing FDA-approved compounds found in common therapies used to treat other diseases, such as type-2 diabetes. This new potential inflammation therapy would be used as a co-therapeutic to common antifungal therapies.

Dr. Peters and his team recently published research that the activation of a signaling pathway, termed the inflammasome, is involved in the vaginal inflammatory response to Candida albicans, the fungal pathogen responsible for VVC. The inflammasome complex senses these pathogens, yet only induces a molecular response in the presence of danger. As such, Dr. Peters and his team have worked with FDA-approved compounds that block the assembly of the inflammasome complex in the hopes of reducing the inflammation that occurs during VVC.

“What’s interesting about VVC is that the immune response is actually what causes the symptoms and is not protective for reasons that aren’t very well understood,” Dr. Peters said. “So, the angle that we have taken is to use an immunomodulatory therapy to try to dampen the inflammation that’s involved in the pathogenesis of the disease to more timely arrest disease symptoms.”

This R21 grant provided to Dr. Peters from the National Institutes of Health (NIH) affords him and his lab two years of funding to continue research on his project entitled, “Sulfonylureas as Repurposed Agents Against Vulvovaginal Candidiasis.”

Though it may be too early to definitively predict an effect this study will have on future research, Dr. Peters believes that upon identifying the best compounds for blocking inflammation, he can potentially extend this discovery to a clinical study to look at the effectiveness of the compound in a human population and open the door for opportunities to rebrand the compounds for alternative use. “That’s the benefit of repurposing a drug that has already been approved,” Dr. Peters said. “It is likely safe and will not cause toxicity because it’s already approved for human use. It would also probably be able to get to market quicker.”

The first-year aim for Dr. Peters is to look at a class of FDA-approved Sulfonylurea compounds, and then screen them in in-vitro models, where he and his team will specifically look for inflammasome-specific inhibition to see what compounds block inflammation effectively and determine optimal dosing. The second-year aim is to use an in-vivo infection model of VVC, in which Dr. Peters and his team will administer compounds or a control vehicle selected from the first aim to see if they can inhibit the inflammation that occurs. “We’ve done this quite a bit with one of these compounds, and results are promising,” Dr. Peters said. “So, we want to figure out which of these compounds is optimal to use and also how we can reduce incidence of symptomatology when we co-administer antifungal therapies to get synergistic effects.”

Dr. Peters is thrilled by this line of research because although VVC is a disease that has been classically understudied due to its treatability, the potential outcome of this project remains huge and crucial, as VVC causes major quality of life issues for an overwhelming population of women. “I’ve been at UTHSC for about two and a half years and was recruited here as part of a growing fungal pathogenesis unit. It is incredibly strong. We have a wonderful group of people here who are well-funded, creative, and fun,” Dr. Peters said “We’re doing good things over here in the College of Pharmacy.”