Repurposing Ethoxzolamide as a New Tuberculosis Therapeutic

F. Urban
Spartan Innovations, Michigan, United States

Keywords: infectious disease, tuberculosis, mycobacterium, therapeutic, drug

Tarn Biosciences, Inc. headquartered in East Lansing, Michigan is developing ethoxzolamide (ETZ) as an adjunct therapy for the treatment tuberculosis (TB). Ethoxzolamide (ETZ) is a carbonic anhydrase inhibitor (CAI) originally approved as a diuretic and anti-glaucoma drug in the late 1950’s. After screening more than 220,000 compounds in a whole-cell reporter assay, the Robert Abramovitch laboratory at Michigan State University (MSU) identified ETZ as an inhibitor of the “PhoPR regulon” pathway essential for Mycobacterium Tuberculosis (Mtb) virulence. The PhoPR regulon is required for growth only in macrophages and in vivo. Consequently, ETZ was found to be unique in its ability to inhibit Mtb growth in vitro in macrophages and in vivo in infective mice. The current treatment of TB involves 6 months or longer of treatment with a combination of several of drugs. This long duration of treatment and combination of drugs is required to effectively treat Mtb entrenched in macrophage granulomas that protect the pathogen from drug therapy. ETZ thereby, holds significant promise as an adjunct TB therapy for simplifying and shortening the course of treatment to improve patient compliance and limit the evolution and spread of multi-drug resistant TB (MDR-TB).