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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (14623)	12/10/2004 9:15:13 AM
From: Biomaven	Read Replies (1) \| Respond to of 52153

This is potentially really fantastic news - TB and malaria are the two biggest under-served medical areas in my view: From today's Science: New TB Drug Promises Shorter Treatment A newly discovered compound may dramatically reduce the amount of time it takes to cure tuberculosis. It also appears to work against multidrug-resistant strains of the bacterium that cause the disease, researchers report online today in Science. Directly observed. TB clinics, like this one in India, monitor drug taking to ensure that patients complete the long course. A chief reason that tuberculosis persists as a global killer--and is on the rise in parts of the world--is that existing antibiotics require up to 9 months of daily use, making it difficult for people to complete the treatment. Those who miss doses, in turn, fuel the emergence of drug-resistant strains of the mycobacterium that causes the illness. Yet the only new TB drugs to become available during the past 4 decades have been variations of the existing ones. Now, researchers at Johnson & Johnson (J&J) in Belgium led by microbiologist Koen Andries report that extensive studies in the test tube and mice have shown that a compound dubbed R207910 is more potent than existing drugs, stays in the body longer, and works by a novel mechanism that makes it broadly effective. Experiments in a few uninfected humans and toxicology studies in rats and dogs so far suggest that the compound is safe. While screening for a new broad-spectrum antibiotic, J&J researchers discovered that a class of compounds called diarylquinolines worked against Mycobacteria smegmatis, a cousin of TB. Chemical tinkering led them to the even more potent R207910. As expected, resistance to R207910 developed when given to mice as a monotherapy, but the J&J team's experiments with mice have convinced leading TB researchers that swapping the drug for one of the three in the most popular triple-drug combination now used would delay development of resistant strains. Some of the combinations rid internal organs of the bug in just 2 months, about half the time it takes using the standard treatment. "This is quite frankly an astonishing set of results," says Denis Mitchison of St. George's Hospital Medical School in London. Researchers are also intrigued by the drug's novel mechanism of action. Additional work suggested that the drug targets ATP, which provides energy for cells. "Nobody before has identified that as a drug target for TB," says William Jacobs of the Albert Einstein School of Medicine in New York City. .... A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis Science 2004 0: 1106753 <snip> Tuberculosis has been increasing significantly on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (MIC 0.06 µg/ml). In mice, R207910 exceeds the bactericidal activities of isoniazid and rifampin by at least 1 log. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid and pyrazinamide) with R207910 accelerates bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibits mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice are well tolerated in healthy human volunteers. Mutants selected in vitro suggest the proton pump of ATP synthase to be the target for the drug.