Research Digest

Lab notes: Asthma drug can help treat TB and counter antibiotic resistance

The drug targets metabolic pathways essential for survival of the TB pathogen.

In their search for new drugs against tuberculosis which is increasingly becoming resistant to presently available drugs, researchers are exploring all options. Scientists at the Indian Institute of Science in Bangalore have found that an existing anti-asthma drug is effective against tuberculosis and can help address the problem of drug resistance as well.

The researchers, through extensive studies, have found that the drug Pranlukast destroys a specific metabolic pathway in Mycobacterium tuberculosis, the causative agent of TB, which is crucial for its survival in human cells. And it does so without causing any damage to host cells. The pathway was till now not known as a drug target for TB.

Traditionally, drugs are used to prevent ability of bacteria to replicate in their host – human body – but this has adverse effects on host cells. In order to overcome this problem, researchers looked for an agent that targets metabolic pathways essential for survival of the TB pathogen. They found that the pathogen used a mechanism called arginine biosynthesis is essential for its survival, and if it is inhibited the pathogen would die. Pranlukast fitted this role.

“Our approach involves targeting tuberculosis in a two-fold manner. We have discovered that Pranlukast acts as a potent inhibitor against M tuberculosis, and have demonstrated that it works by directly targeting the pathogen as well as subverting its strategies to conquer within the host,” said Archita Mishra, who did the work as part of her PhD under Professor Avadhesha Surolia.

The drug targets a unique arginine biosynthesis enzyme which is exclusive to Mtb, thereby impeding its arginine production. It also targets the pathogen pro-survival pathways in the host, directly reducing intracellular survival of the TB bacteria.

Since Pranlukast is an FDA approved molecule and is already being used as an anti-asthmatic drug in various parts of the world, it has the potential to be included directly into the therapeutic regime against TB. “Our work proposes a combination of Pranlukast with the standard-of-care therapy drugs, to be highly efficient against TB pathogen, thereby providing an opportunity to use this novel drug combinations for TB therapeutics,” explained Surolia. The results of the study have been published in journal EMBO Molecular Medicine.

The work also demonstrates how new drug discovery cycle can be shortened. “In contrast to conventional drug discovery methods, we employed the ‘drug repurposing’ approach wherein FDA-approved drug datasets are used for screening. This significantly shortens the screening timeline and also suggests human safety of such drugs molecules,” explained Mishra.

The combinations tested have shown that smaller concentrations of standard TB drugs would be needed when used along with Pranlukast. The results have also not shown any side effects in animal studies. The drug is already in market as an anti-asthmatic drug and is safe for human consumption.

“We are further exploring the detailed mechanism of action of Pranlukast to get deeper insights in pre-clinical models. Since it is an FDA approved drug we are also planning to engage with clinical collaborators for trials in future,” Surolia added.

The study is supported by grant from Department of Science and Technology and partially from the Council of Scientific and Industrial Research, Indian Council of Medical Research , and Department of Biotechnology.

The research team included Archita Mishra, Ashalatha S Mamidi, Raju S Rajmani, Ananya Ray, Rajanya Roy and Avadhesha Surolia.

This article was first published by India Science Wire.

Support our journalism by subscribing to Scroll+ here. We welcome your comments at letters@scroll.in.
Sponsored Content BY 

Following a mountaineer as he reaches the summit of Mount Everest

Accounts from Vikas Dimri’s second attempt reveal the immense fortitude and strength needed to summit the Everest.

Vikas Dimri made a huge attempt last year to climb the Mount Everest. Fate had other plans. Thwarted by unfavourable weather at the last minute, he came so close and yet not close enough to say he was at the top. But that did not deter him. Vikas is back on the Everest trail now, and this time he’s sharing his experiences at every leg of the journey.

The Everest journey began from the Lukla airport, known for its dicey landing conditions. It reminded him of the failed expedition, but he still moved on to Namche Bazaar - the staging point for Everest expeditions - with a positive mind. Vikas let the wisdom of the mountains guide him as he battled doubt and memories of the previous expedition. In his words, the Everest taught him that, “To conquer our personal Everest, we need to drop all our unnecessary baggage, be it physical or mental or even emotional”.

Vikas used a ‘descent for ascent’ approach to acclimatise. In this approach, mountaineers gain altitude during the day, but descend to catch some sleep. Acclimatising to such high altitudes is crucial as the lack of adequate oxygen can cause dizziness, nausea, headache and even muscle death. As Vikas prepared to scale the riskiest part of the climb - the unstable and continuously melting Khumbhu ice fall - he pondered over his journey so far.

His brother’s diagnosis of a heart condition in his youth was a wakeup call for the rather sedentary Vikas, and that is when he started focusing on his health more. For the first time in his life, he began to appreciate the power of nutrition and experimented with different diets and supplements for their health benefits. His quest for better health also motivated him to take up hiking, marathon running, squash and, eventually, a summit of the Everest.

Back in the Himalayas, after a string of sleepless nights, Vikas and his team ascended to Camp 2 (6,500m) as planned, and then descended to Base Camp for the basic luxuries - hot shower, hot lunch and essential supplements. Back up at Camp 2, the weather played spoiler again as a jet stream - a fast-flowing, narrow air current - moved right over the mountain. Wisdom from the mountains helped Vikas maintain perspective as they were required to descend 15km to Pheriche Valley. He accepted that “strength lies not merely in chasing the big dream, but also in...accepting that things could go wrong.”

At Camp 4 (8,000m), famously known as the death zone, Vikas caught a clear glimpse of the summit – his dream standing rather tall in front of him.

It was the 18th of May 2018 and Vikas finally reached the top. The top of his Everest…the top of Mount Everest!

Watch the video below to see actual moments from Vikas’ climb.

Play

Vikas credits his strength to dedication, exercise and a healthy diet. He credits dietary supplements for helping him sustain himself in the inhuman conditions on Mount Everest. On heights like these where the oxygen supply drops to 1/3rd the levels on the ground, the body requires 3 times the regular blood volume to pump the requisite amount of oxygen. He, thus, doesn’t embark on an expedition without double checking his supplements and uses Livogen as an aid to maintain adequate amounts of iron in his blood.

Livogen is proud to have supported Vikas Dimri on his ambitious quest and salutes his spirit. To read more about the benefits of iron, see here. To read Vikas Dimri’s account of his expedition, click here.

This article was produced by the Scroll marketing team on behalf of Livogen and not by the Scroll editorial team.