Heartburn Drug Lansoprazole May Fight Tuberculosis Too

The over-the-counter drug lansoprazole—Takeda’s Prevacid—has long been used as a treatment for frequent heartburn. But new research suggests the proton pump inhibitor, which limits the stomach’s manufacture of gastric acid, may also be a prodrug for a compound effective against Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Because of increasing drug resistance, there is a pressing need for new TB drugs. So researchers led by Stewart T. Cole of the Swiss Federal Institute of Technology (ETH), Lausanne, developed a new method of high-throughput screening to test a set of FDA-approved drugs for activity against the bacterium (Nat. Commun. 2015, DOI: 10.1038/ncomms8659). Although most screens look for antimicrobial activity in a bacterial broth, the new method screens assay results on fibroblasts to better address intracellular M. tuberculosis found in the body. In cells, lansoprazole undergoes sulfoxide reduction, and its metabolite, lansoprazole sulfide, kills the bacterium. When Cole’s team orally administered lansoprazole sulfide to infected mice, severity of the TB infections was significantly reduced. “This is a very exciting paper that demonstrates the importance of rescreening old FDA-approved drug libraries using new techniques,” says Eric Oldfield, a TB researcher at the University of Illinois, Urbana-Champaign.