Working towards personalised TB treatment

Three major global research centres in India will receive funding coming out of collaboration between the UK Medical Research Council (MRC) and the Department for Biotechnology (DBT), India. The Department for Biotechnology will match the funding provided by UK through MRC and Newton Fund.

The Chennai-based National Institute for Research in Tuberculosis (NIRT) will get one million pounds in funding from UK and DBT will provide an equivalent amount over a three-year period to develop new diagnostic tools and new treatments to address the sharp rise in cases of multi-drug resistant tuberculosis (MTB). The initiative will start in May/June this year.

“We will be undertaking whole genome sequencing of the TB bacterium to see the pattern of drug resistance in the community,” said Dr. Soumya Swaminathan, Director of NIRT. “As of now, there is limited information on drug resistance for second-line drugs and newer drugs.”

A UK company has already developed a cheap, hand-held, robust tool that has the capacity to carry out whole genome sequencing. The testing and validation of the chip-based technology will be done in India. “Within three years, we will be using this technology in India to sequence the genome of patients so that personalised TB treatment can be offered for better outcomes,” she said.

Many patients with MDR-TB and XDR-TB are resistant to second-line drugs. The new technology will help in finding out the mutations in a patient and decide a treatment that is tailor-made for him.

The second part of the funding will be for translational work. “It will mainly focus on host-directed therapies to improve the host’s immune system,” Dr. Swaminathan said.

Cambridge University has already identified some available drugs used for other diseases to target different pathways in immune response to fight the TB bacteria. The basic work has already been done.

A drug (verapamil) used for treating BP effectively blocks the efflux pump of the TB bacteria. Efflux pump pushes out a drug from the bacteria thus making the drug ineffective. Other drugs target TB bacteria by increasing autophagy, thereby killing them.

The second collaboration is between the Hyderabad-based L.V. Prasad Eye Institute and University of Sheffield. The collaboration is for developing and testing a technology that can be used for treating ocular infections.

“This technology has the potential to be used for other infections as well,” said Dr. Proshant Garg, Director and G. Chandrasekhar distinguished Chair of Education at the Institute.

The technology uses a highly functionalised polymer that can bind to specific microorganisms. Nanoparticles containing the antibiotics will be first tagged to the polymer with the hope that the polymer will deliver the nanoparticles to the site of infection. Once the polymer binds to the bacteria, the nanoparticles will release the antibiotics into the immediate environment of the microorganism.

“It’s a kind of missile technology for targeted drug delivery,” Dr. Garg said. The polymer, which will act as a drug carrier, has already been developed by the Institute in 2010-11 and its specificity to binding on microorganisms has also been verified.

“The collaboration will develop the technology to attach the nanoparticle to the smart polymer,” he said. The other pending work is to develop nanoparticles of different antibiotics and attach them to the polymer and ensure that the combination moves into the tissue and reaches the site of infection.

MRC will be providing Rs.9 crore and DBT’s share will be Rs.3 crore. The grant duration is four years.

Published in The Hindu on February 19, 2015