Indian scientist’s discovery may lead to TB drug breakthrough

An Indian scientist has discovered a molecule which he claims can be a harbinger for a single drug therapy to treat tuberculosis and replace the current costly multi-drug treatment for the killer disease. “TB bacteria has a complex coat over its surface which is unique. We, through our research, have been trying find the enzyme that helps in forming the upper layer of the bacterium,” Rajesh Gokhale of the National Institute of Immunology said in Delhi. A team of researchers led by Gokhale found that the new molecule hits four of the bacterium crucial metabolic pathways at the same time, weakening and ultimately destroying the pathogen. “Right now, tuberculosis patients take a cocktail of four drugs and each inhibits a single enzyme,” said Gokhale, a Howard Hughes Medical Institute research scholar. “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.” But the research, which is at the preliminary test tube level, needs funding for the next step. “The enzymes have to be tested on animals for the new findings to turn into drugs for human use,” said Gokhale. “We are trying to identify international NGOs and pharma companies to collaborate with us in the project,” Gokhale said.The multi-drug regimen is a major problem as it requires TB patients to manage taking four drugs exactly as prescribed over six to nine months but any missed dosage can lead to the resistant TB bacteria which is difficult to treat. Gokhale said a single drug that targets multiple pathways can save time and money by eliminating the need to take so many drugs over such a long period of time. To create their new compound, Gokhale and his colleagues exploited an evolutionary quirk in the way Mycobacterium Tuberculosis builds the lipid layer that coats its surface. For the past seven years, Gokhale and his colleagues have studied the intricate metabolic pathways that Mycobacterium Tuberculosis employs to build complex lipids. “A major challenge has been to develop drugs that can target different stages disease,” Gokhale said. “Since this single molecule could potentially grind the assembly line to a halt at different stages of infection, this approach provides tremendous opportunity to develop unique anti-tuberculosis drugs,” he said. He has also collaborated with researchers at Centre for Cellular and Molecular Biology in Hyderabad to examine the three-dimensional structure of the molecule.

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