New candidate drugs for resilient form of TB

Scientists have found two new candidate drugs that could fight the most resilient form of tubercolosis (TB), which has emerged as one of the world's major public health threats.

The candidates – NITD304 and NITD349 – look promising in the battle against the multi-drug resistant tuberculosis, in combination with other medicines.

Currently, doctors do not have a lot of options against this form of tuberculosis. With an estimated 64,000 MDR-TB cases in 2012, India is one of the world’s hotspots in drug-resistant TB due to the large number of patients that drop out of the government-monitored revised national TB control programme.

“People are missed because they do not seek care in the public sector. Most patients first seek care in the informal and private sector, and may eventually end up in the public sector when they run out of money,” said Madhukar Pai, a TB researcher at McGill University, Montreal.

Since the new molecules act differently in the body, they would be effective against tuberculosis-causing bacteria which acquired resistance against the current set of drugs because of their misuse over decades, said Ujjini Manjunatha, a senior investigator in the drug discovery unit at Novartis Institute for Tropical Diseases (NITD), Singapore.

The NITD, along with three other Novartis-funded institutes, reported the discovery in the December 4 issue of Science Translational Medicine.

“The two molecules were effective in treating tuberculosis infections in mice and did not exhibit any adverse side effects. The prospect of combining them with existing TB drugs, or other new candidates, offers hope for the a more efficacious and safer drug regimen,” said Manjunatha, who did his early education in Bellary and got a PhD from the Indian Institute of Science, Bangalore.

Novartis scientists claim that the effective dose of these compounds in humans would be about 5 mg per kg of body weight per day. Independent researchers, however, questioned the dosage.

“The molecules showed promise, though more work is needed. I am also not convinced if they would be a once-daily kind of medicine. There are several questions to be answered,” Tanjore Balganesh, an adviser to the Council of Scientific and Industrial Research’s Open Source Drug Discovery programme, told Deccan Herald.

After almost four decades of lull, there are now several candidate drugs against MDR-TB in the laboratory.

“The biggest challenge for the industry is to differentiate, which one of them will work best and develop that molecule further,” said Balganesh, who is not associated with the Novartis study and was formerly a senior scientist for pharmaceutical company AstraZeneca.

One of the new molecules – Bedaquiline – was approved by the US Food and Drug Administration to treat MDR-TB cases few months ago, whereas a second molecule – Delamatib – received regulatory approval for large-scale trials just a few days ago.