Testing thousands of approved drugs, researchers have identified an unlikely anti-tuberculosis drug: the over-the-counter antacid lansoprazole (Prevacid®).
Tuberculosis continues to be a global pandemic, second only to AIDS as the greatest single-agent killer in the world. In 2013 alone, the TB bug Mycobacterium tuberculosis caused 1.5 million deaths and almost nine million new infections. Resistance to TB drugs is widespread, creating an urgent need for new medicines. Researchers have now identified lansoprazole, a widely used, over-the-counter antacid, as an excellent candidate against tuberculosis. The study is published in Nature Communications.
It takes well over ten years for a new tuberculosis drug to be approved for human use. Meanwhile, traditional antibiotics have led many strains of tuberculosis bacteria to evolve multi-drug resistance. Millions of new chemical compounds have been tested for their ability to disrupt the growth of M. tuberculosis in the test tube, but discouragingly few are currently in clinical trials.
But we can speed this process up. Compounds that have already been approved for use in humans could be repurposed as anti-tuberculosis medications, and cut down both the time and cost of new drug development.
The researchers used a robotized system that gives candidate drugs to cultured lung cells that have been infected with M. tuberculosis. The scientists screened a large panel of already approved drugs, and identified the blockbuster antacid lansoprazole, known commercially as Prevacid®, as a potential anti-tuberculosis medication.
Lansoprazole was found to be effective against M. tuberculosis but only when the bacterium grows inside cells. The researchers investigated the underlying biology and found that lansoprazole kills the bacterium after the human cells convert it into a sulfur-containing metabolite. This metabolite targets a particular enzyme that is crucial for the bacterium to produce energy, thereby killing it off. In addition, when the scientists tested lansoprazole against a wide range of other bacteria, it proved to be highly selective for M. tuberculosis.
Lansoprazole belongs to a class of drugs known as "proton-pump inhibitors" that keep the stomach from pumping too much acid, thus preventing heartburn and ulcers. "Proton-pump inhibitors are both safe and widely sold around the world," the researchers said. "Being highly active against drug-resistant strains of M. tuberculosis, this novel class of drugs provides us with an excellent opportunity to treat tuberculosis."
Based on material originally posted by Ecole Polytechnique Fédérale de Lausanne.
Rybniker J, Vocat A, Sala C, Busso P, Pojer F, Benjak A, Cole ST. Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nature Communications 07 July 2015. DOI: 10.1038/ncomms8659