Indian researcher creates compound that knocks out TB pathogen

February 2nd, 2009 - 2:49 pm ICT by IANS  

Washington/New Delhi, Feb 2 (IANS) An Indian researcher has created a compound that knocks out four of the tuberculosis bacterium’s crucial metabolic pathways simultaneously, ultimately crippling the pathogen. The development opens the way to designing a single drug that is safe and effective, and may replace the costly cocktail of drugs that people with tuberculosis (TB) must currently take to cure their disease.

TB remains one of the world’s top 10 killers, claiming nearly two million people every year worldwide and roughly 1,000 people daily in India, according to the World Health Organisation (WHO).

“Right now, tuberculosis patients take a cocktail of four drugs, and each inhibits a single enzyme,” said Rajesh Gokhale, Howard Hughes Medical Institute research scholar based at the National Institute of Immunology in New Delhi, India.

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 take the full course of the medicines, the TB bacteria may develop resistance to the drugs and become even more difficult to treat.

To reduce that risk, many countries require that patients go to a clinic so a healthcare professional can watch them take the medication and ensure they are complying with their drug-treatment regimen. This is both expensive and time consuming.

A Howard Hughes release quoted Gokhale as saying that a single drug that targets multiple pathways could save time and money by eliminating the need to take so many drugs over such a long period of time.

“Since this single molecule (compound) could potentially grind the assembly line to a halt at different stages of infection, this approach provides tremendous opportunity to develop unique antituberculosis drugs,” he said.

Gokhale has collaborated with a colleague at the Centre for Cellular and Molecular Biology in Hyderabad, Rajan Sankaranarayanan, to examine the three-dimensional structure of the molecule.

This will give his group the opportunity to modify the molecule or develop a new one that is less toxic and better targets the TB bacteria.

Gokhale said the drug industry is finally waking up to the idea that a single drug can work on multiple metabolic pathways, rather than making a molecule that acts in a very specific way on a single target.

“The ‘one disease - one drug - one target’ paradigm that has dominated thinking in the pharmaceutical industry for the past few decades is now being increasingly challenged by the discovery of compounds that bind to more than one target,” Gokhale said.

“That’s the direction we’re heading in trying to develop a single chemical entity that could simultaneously target a family of enzymes in TB,” he added.

These findings were published in the January issue of Nature Chemical Biology.

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