Features Monday, February 02, 2015 - 05:30
Chitra Subramaniam | The News Minute | February 2, 2015 | 01:11 pm IST Follow @chitraSD If the new protein discovered by Indian scientists fulfills the promise it currently holds, Make in India in the pharmaceutical sector will go to an entirely new dimension. A team of Indian scientists led by Drs Anand Ranganathan and Pawan Malhotra from the International Centre for Genetic Engineering and Biotechnology (ICGEB) Delhi has discovered a novel peptide (type of protein) that could be the next-generation cure for Tuberculosis (TB) and Malaria two of India’s major killer diseases. Their discovery, published in the January 2015 issue of the high-impact journal Nature Communications, offers a critical way forward in the global fight against the tuberculosis superbug and the dreaded malaria parasite. Read the article in Nature here: Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum “Drug resistance is a major issue in treating TB – the protein we have discovered addresses that threat in a significant way. While these are early days, we are very encouraged by the results of our research,” Ranganathan told The News Minute (TNM). The World Health organization (WHO) estimates that there are some seven million cases of TB reported worldwide out of which 2.2 million are in India alone. In 2012, the disease killed 1.3 million people worldwide and India accounted for 26 percent of the total number of deaths. The same year India declared TB to be a notifiable disease making it mandatory for all private doctors, care-givers and clinics treating the disease to report every case to the government. Reporting, tracking and tracing along with resistance to available drugs looms large over India’s burden of disease. Avoidable stock-outs of drugs make a bad situation worse. (Anand Ranganathan) The breakthrough Ranganathan and his team of scientists have developed a way of arresting infection that bypasses the bug completely, thereby alleviating the worry about its strain – resistant or the non-resistant type. From scratch, their team has engineered a protein called M5 which targets human cells that play host to the bugs. What is most unique about M5 is that it works by latching on to a variety of human proteins called Inter-Cellular Adhesion Molecules (ICAMs) that help several pathogens gain entry into human cells. This done, M5 becomes a powerful drug-like molecule against several bug-host combinations. In their current published work, the Delhi scientists have shown infection elimination of resistant strains of TB and malarial bugs by as much as 80%. “This work forms the framework for the development of a single drug for combating two deadly infectious diseases, namely Malaria and Tuberculosis, where wide-spread drug resistance is rampant,” says Pawan Malhotra. “In future, M5’s range can be extended to other dreaded pathogens such as HIV-1 for AIDS, Human Rhinoviruses (HRV) for flu, and more,” adds Anand Ranganathan. While it may be some time before such peptide-based drugs are widely seen in the market, this study paves the way for identifying and targeting host-specific molecules for treatment of infectious diseases. Enabling environment and research In the ongoing battle against infectious diseases, scientists around the world continue to search for new therapeutic inventions especially to counter the emerging and proliferating antibiotic resistance in pathogens. The Indian discovery was made possible by recent research on chip-based screening of the entire human genome which pointed to the fact that targeting human proteins that are utilized by pathogens to gain entry or invade and survive inside a human cell may be the way forward in the search for such new drugs. This is because resistance is no longer a worry as the pathogen is not a direct target but the mechanism by which it enters the human cell is. “Crucially, the ability of our synthetic polypeptide to target the human ICAM proteins was what revealed their hitherto unknown involvement in invasion by the tuberculosis and malaria pathogens respectively,” Ranganathan said. Uniqueness of discovery What is most unique about this discovery is that the same polypeptide targets two structurally similar human proteins, albeit expressed on different host cells, inhibiting the invasion of two very different pathogens significantly and comparably. Ranganathan says the findings of the study are important as the polypeptide also successfully inhibits invasion by resistant strains of the malarial pathogen. By targeting human proteins to fight the mutation the Indian scientists have discovered a completely synthetic polypeptide that interacts with a human protein and inhibits infection by as much as 80% of pathogens that cause tuberculosis and malaria. Read more about the human protein called ICAM 1 and its homologue here. In the case of the malaria causing parasite Plasmodium falciparum, the infection is prevented across resistant strains. This aspect is especially important as the currently available drugs for treatment of both malaria and tuberculosis have been failing in cases with resistant strains of pathogens causing wide-spread alarm. (Lead student Kuhulika Bhalla) Treatment of tuberculosis today Tuberculosis is currently treated with antibiotics with an offensive warfare approach targeted directly against the bug. A regimented army of antibiotics is administered on a patient to invade and kill as many TB bacteria as possible in the body. Antibiotics have been used as TB drugs for the past 70 years (Streptomycin since 1944 and Rifampicin since 1963). Despite this, success has slowed down principally because the TB bug transforms itself into a super-bug that outsmarts antibiotics by developing resistance against them. Drug resistant strains The resistant varieties of TB bacteria are called MDR (Multi Drug Resistant) or XDR strains. The first resistant strain was detected in the late 40s. There has been no new major anti-TB drug for the past 50 odd years. Malaria in another killer facing similar challenges of emerging parasite resistance to antimalarial medicines and mosquito resistance to insecticide, which if left unaddressed, could render some of the current tools ineffective and trigger a rise in global malaria mortality (WHO World Malaria Report 2014) The new drug-discovery could change all in India and around the world. Tweet Follow @thenewsminute

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