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Scientists determine drug target for the most potent botulinum neurotoxin
Date:4/29/2008

UPTON, NY Botulinum neurotoxin responsible for the deadly food poisoning disease botulism and for the beneficial effects of smoothing out facial wrinkles can also be used as a dreaded biological weapon. When ingested or inhaled, less than a billionth of an ounce can cause muscle paralysis and eventual death. Although experimental vaccines administered prior to exposure can inhibit the destructive action of this neurotoxin the most deadly protein known to humans no effective pharmacological treatment exists.

Now, scientists at the U.S. Department of Energys Brookhaven National Laboratory and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have taken the first step toward designing an effective antidote to the most potent form of the toxin. They have found that they can trick the toxin to bypass its normal binding protein, thereby blocking its deadly action. The results of their research are reported in the April 22, 2008 online issue of the Journal of Biological Chemistry.

We have found a highly efficient inhibitor of botulinum neurotoxin type A the most potent of seven neurotoxins produced by the bacterium Clostridium botulinum. This finding can lead to a very effective drug to stop the devastating effects of the toxin, said Brookhaven Lab biologist Subramanyam Swaminathan, the studys co-principal investigator. We intend to do further research to tailor the inhibitor for the best results.

We are excited about the success of this work and the prospects it holds for future drug development, said USAMRIID principal investigator S. Ashraf Ahmed, who initiated the structure-based inhibitor design as part of the Institutes bio-defense research program.

To cause its deadly effects, the botulinum neurotoxin first binds to a nerve cell membrane, which curves inward, incorporating the toxin into a vesicle that drifts inside the cell. The toxin eventually travels from the vesicle to the cytosol, the int
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Contact: Diane Greenberg
greenb@bnl.gov
631-344-2347
DOE/Brookhaven National Laboratory
Source:Eurekalert

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