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In India: A search for more effective tuberculosis drugs
Date:2/1/2009

Rajesh Gokhale has created a compound in his lab in India that stops tuberculosis in its tracks. In a test tube, the molecule hits four of the bacterium's crucial metabolic pathways at the same time, weakening and ultimately destroying the pathogen.

The problem is that Gokhale's compound will not work in humans. Not willing to set aside seven years of work, he has been knocking on the doors of pharmaceutical companies to see if he can get any takers to help design a less toxic version. Gokhale is pushing himself because he knows if he can design a single drug that is safe and effective, it might one day replace the costly cocktail of drugs that people with tuberculosis must currently take to cure their disease.

While a drug based on Gokhale's ideas is still years away from human testing, it offers a measure of hope that researchers may one day have more modern pharmaceutical "weapons" that can slow down the tuberculosis (TB) pathogen's relentless assault. According to the World Health Organization, TB remains one of the world's top-ten leading causes of death, killing nearly two million people each year. In Gokhale's native India, it kills roughly 1,000 people each day.

"Right now, tuberculosis patients take a cocktail of four drugs, and each inhibits a single enzyme," said Gokhale, a Howard Hughes Medical Institute international research scholar based at the National Institute of Immunology in New Delhi, India. Gokhale's group shows how they designed the molecule that targets multiple enzymes in Mycobacterium tuberculosis in the January 25, 2009, issue of Nature Chemical Biology. "Targeting several enzymes at the same time is a much more efficient approach. Theoretically, patients wouldn't have to take several drugs, they could just take one."

The multi-drug regimen is a major problem for several reasons. It requires TB patients to manage taking four drugs exactly as prescribed over six to nine months. If patients don't tak
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Contact: Andrea Widener
widenera@hhmi.org
301-215-8807
Howard Hughes Medical Institute
Source:Eurekalert

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