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New weapon in battle with drug-resistant TB

Researchers at the Novartis Institute for Tropical Diseases have isolated a new class of drugs that could be used to treat drug-resistant tuberculosis, a disease that affects thousands of Cambodians, according to a report published in the journal Science Translational Medicine last week.

The drugs, called indolcarboxamides, work by blocking a protein called MmpL3 that is essential to TB cells’ survival.

“Like a dam keeping back water, the [tuberculosis] cell wall maintains the integrity of the bacterium,” said a news release accompanying the report. “Without MmpL3, the cell wall becomes weak and eventually collapses, killing the cell.”

Because the drugs have a “novel mode of action” in stopping TB, said Dr Manjunatha Ujjini, who took part in the study, “there is no pre-existing resistance, and [they] therefore could prove to be effective against drug-resistant strains of [mycobacterium TB]”.

The new drugs also exhibited a “favourable safety margin” in mice, and are not likely to interact with other drugs, Ujjini said in an email.

“Typically in drug discovery and development it takes a few years (5-6 years) to have a potential impact on the medical community,” he said.

Cambodia has one of the highest prevalences of TB in the world, said Medicins Sans Frontieres Head of Mission Jean-Luc Lambert, but even with the number of cases in the hundreds of thousands, only 14 per cent are drug resistant.

“For regular TB, the treatment is six months, but if you are drug resistant or multi-drug resistant, the treatment can be 16 months up to 24 months, with additional drugs and more side-effects,” Lambert said.

“The most difficult patients to treat are multi-drug resistant, and luckily in Cambodia, these multi-drug resistant patients represent only 2 per cent, which is a low prevalence .”

Rajindra Yadav, a technical officer for TB with the WHO, said that only two drugs for TB had been patented since 1960.

“That’s the worst thing about the TB program. Other programs get new drugs all the time,” he said, noting that things are starting to change. “Now all the pharmaceutical companies are showing interest.”

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