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First drug developed for widespread use against botulism

An eight-year research effort by university and military scientists in the U.S. has produced the first drug that can be mass-produced to prevent or treat botulism, the paralyzing disease caused by a nerve toxin that is considered one of the greatest bioterrorism threats.

The UCSF-led research is being published on line the week of August 5 by The Proceedings of the National Academy of Sciences.

Botulinum toxin, naturally produced by a soil bacterium, is the most poisonous substance known. A gram of the toxin, if evenly dispersed and inhaled, could kill a million people, according to a recent study. Yet no anti-botulism drugs are available which could be produced in the quantities needed for treatment or prevention if the toxin were used for bioterror, the new study points out. The new drug potently neutralizes botulinum toxin and can be readily mass-produced, the researchers report.

The drug was developed by expanding the technique now used to produce monoclonal antibodies against pathogens or other molecular targets. Scientists isolated and identified three antibodies against botulinum toxin and combined them. Each antibody is capable of binding to a different part of the toxin molecule. When administered together, they bind the toxin much more tightly and block far more of the toxin surface than a single antibody could, the scientists report. As a result, in animal studies, the antibody "cocktail" neutralizes much more of the toxin than observed for single antibodies.

Treatment for botulinum poisoning usually requires many weeks of intensive-care hospitalization, and exposure of even a small number of people would seriously disrupt health care delivery in any major city, according to a recent assessment. A vaccine has been developed, but widespread use is not currently being considered, the researchers say, since the likelihood of exposure is uncertain. Also, vaccination would block accepted treatments for a number of overactive mu
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
5-Aug-2002


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