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Experimental TB drug effective against resistant and latent mycobacterium tuberculosis

An experimental tuberculosis drug may be effective against not only multi drug-resistant forms of the disease but could also be the first compound to treat the latent stage of infection as well. Researchers report their results today at the 2006 ASM Biodefense Research Meeting.

"The class of which this compound is the lead has a very different mechanism of action from any other drug currently used to treat tuberculosis. We have identified no cross resistance with existing drugs. Every isolate we have tested so far has been susceptible to this compound," says Nicole Parrish of Johns Hopkins Medical School, a lead researcher on the study.

"This compound (FAS20013) appears to be a potential new drug for treating all forms of tuberculosis, even drug-resistant and latent infections," says Albert Owens, President of FASgen, Inc., the company working to bring the drug to market.

The potent killing activity of FAS20013 is directed specifically against slow growing mycobacteria that cause the disease rather than at a broad array of non-pathogenic organisms, which merely enhances the emergence of drug- resistant strains. No resistance has been encountered to FAS20013 in clinical isolates,. The short-term killing power of FAS20013 is greater than currently used drugs; for example, FAS20013 will kill more organisms in a 4-hour exposure than isoniazid or rifampin can during a 12- to 14-day exposure.

Multiple drug-resistant tuberculosis (MDR-TB) has a fatality rate of 20 to 80 percent. In the United States if a person fails to respond to all therapies and doctors cannot bring the active infection under control, that person must be quarantined indefinitely to prevent the spread of the drug-resistant infection in the population. In the most extreme cases, part of the lung may be surgically removed. It is estimated the cost of treating a single case of MDR-TB can be as much as $250,000.

What makes this drug candidate even more promis ing, says Parrish, is that it may be the first compound ever to treat latent tuberculosis infection as well.

After exposure, tuberculosis often establishes a latent infection, where the infected patient has no symptoms and is not contagious, but could become active at any time. It is estimated that nearly a third of the world's population, approximately 2 billion people, are latently infected.

"The latently infected represent an enormous reservoir for future outbreaks. Existing drugs are ineffective at targeting latent infection. In laboratory assays our compound is lethal to latently adapted Mycobacterium tuberculosis," says Parrish.

The researchers are currently undertaking animal experiments that examine pharmacology and toxicology in preparation for an investigational new drug (IND) application to the Food and Drug Administration, which they hope to submit in a few months, so they may proceed to clinical trials.

If the drug lives up to the promise in human trials that it showed in the laboratory, it could be available for treatment of MDR-TB in two to three years, says Owens.


Source:American Society for Microbiology

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