Bengaluru:

Three scientists from Bengaluru, who led a team of global researchers looking for an antimalarial drug, have found a fast-killing solution. After completing some tests, it’ll go in for clinical trials on humans. That this drug has the potential to cure the dreaded disease in one dose makes it more attractive to healthcare providers. The Bengaluru solution — Triaminopyrimidine (TAP) — comes with many advantages over existing drugs. Vasan Sambandamurthy, one of the senior authors of the research paper, said: “It’s a fast-killing and long-acting antimalarial clinical candidate. TAP acts exclusively on the blood stage of Plasmodium falciparum (the stage responsible for clinical symptoms) in a relevant mouse model. This candidate is equally active against causative agent Plasmodium vivax.” He added, “The compound has shown good safety margins in guinea pigs and rats. With a predicted half-life of 36 hours in humans, TAP offers potential for a single dose combination.” The rapid spread of Plasmodium falciparum, the parasite which causes malaria in humans, has left nations battling it with a weakened arsenal and coping with thousands of deaths every year. This parasite has gradually become resistant to available medication. The World Health Organisation (WHO) estimates that 3.2 billion people in 97 countries, including India, are at risk of being infected with malaria. In 2013, WHO reported an estimated 198 million cases and the disease was responsible for an estimated 5.84 lakh deaths, including 4.53 lakh children less than five years old. Every person infected with malaria has to deal with millions of parasites and existing drugs have a limited effect in humans. “The half-life, which isn’t more than 2 hours, means it allows parasites to bounce back. Existing drugs are not fast-killing, which means that not only does a human need more doses but each dose is capable of only killing a few parasites,” he said.

Besides, a potential side-effect of existing drugs is liver damage. “This doesn’t happen all the time, but the possibility does exist. Also, the parasites have become resistant to these drugs. With TAP, there are now known side-effects and the parasites are unable to develop resistance at the same pace as they do for existing drugs,” he said. TAP was discovered by a team at pharmaceutical company AstraZeneca. “The main research happened in its R&D centre in Bengaluru between 2011 and 2014), which has since been shut down. It took us three years of rigorous work by teams across the globe. Today, we confidently nominate TAPs as a clinical candidate to treat drug-resistant malaria,” Vasan said. Shahul Hameed and Suresh Solapure were the two other team leaders.
Active against drug-resistant malaria TAP has a novel mechanism of action that specifically inhibits targets a protein involved in maintaining specific and localised agents that serve as the major route to disturb the proton gradient inside the parasite hydrogen ion levels. Vasan Sambandamurthy | researcher

Global work, delivered in Bengaluru The project was partnered and partially funded by Medicines for Malaria Venture (MMV) based in Switzerland. This work showcases collaboration among big pharma companies (AstraZeneca, Glaxo Smith Kline) and several labs worldwide (Columbia University, Harvard Medical School) for a disease highly prevalent in the developing world. The research was primarily conducted at AstraZeneca’s R&D center, Bengaluru, while safety and toxicology studies supported from its other sites. While Glaxo Smithkline, Spain conducted some of the proof of concept studies, Columbia University, New York and Harvard School of Public Health did the target identification studies.

source: http://www.timesofindia.indiatimes.com / The Times of India / Home> City> Bengaluru / by Chetan Kumar, TNN / May 01st, 2015