The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be the development of an engineered probiotic as an treatment for hyperuricemia and gout. Acute gout episodes cause debilitating pain and hypersensitivity, seriously impairing mobility. Over time, joint damage and deformity, chronic usage-related pain, and disfigurement follow. Although gout can be treated by drugs that lower uric acid levels, these drugs have significant drawbacks for many patients: they have limited effectiveness, are associated with serious side effects, and may be expensive. Gout patients experience an estimated increase of 5 absence days annually with an incremental cost of $3, 000 per patient. The 9.2 million gout patients in the USA spend more than $1.3 billion per year on gout drugs. Moreover, roughly half take additional supplements. The proposed project will develop a novel probiotic strain to address hyperuricemia. This Small Business Innovation Research (SBIR) Phase I project will advance hyperuricemia treatment using an engineered probiotic. The proposed treatment is based on the observation that enzymatically degrading uric acid in the intestine reduces serum uric acid levels, unlike conventional treatments targeting the circulatory system, the urinary tract, or function systemically. This project will use genetic screening to identify a probiotic strain to break down uric acid, engineering it to prevent gene mobility across species and avoid transfer of antibiotic resistance to the intestinal microbiome. Finally, we will confirm safety and efficacy in a mouse model of hyperuricemia. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
