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New Drug Neutralizes Anthrax Toxin in Rats

After the recent cases of anthrax infection reported in Florida and New York, the dearth of vaccine against this potentially deadly disease is more worrisome than ever. There are other strategies on the horizon to fight anthrax, though. In this month's Nature Biotechnology, researchers at Harvard Medical School publish the first results in rats of a drug designed to neutralize the toxin that makes anthrax infection lethal.

When R. John Collier and his co-workers simultaneously injected rats with 10 times the lethal dose of anthrax toxin and a toxin inhibitor developed in Collier¿s lab, the animals' symptoms were delayed or didn't appear after one week, depending on how much of the drug they were given. They were also protected by antitoxin injected three to four minutes later. Such rats normally die within a few hours of exposure to anthrax. The drug still has to be tested against whole bacteria, but this initial result suggests the drug or something like it "could be a useful therapeutic ally against clinical anthrax," Collier and co-workers write.

Antibiotics can kill the anthrax bacterium, but the toxin it secretes, which actually causes symptoms and kills host cells, may already be present in lethal amounts by the time the drugs are administered. Anthrax toxin is composed of a protein-digesting enzyme, or protease, and seven small pieces that attach to the host cell, forming a pore. After the cell unwittingly swallows the toxin, the protease enzyme slides through the pore and into the cell to chew up its innards. The antitoxin consists of more than 20 linked copies of a small protein that latch onto the pore, preventing the protease from getting inside the cell.

Collier published earlier this year in Science on another antitoxin¿an altered form of the protein that makes up the pore¿which seems to be even more effective, he tells Scientific American. It would be hard for a bioterrorist to find a strain of anthrax that could resist either approach, he adds, because the toxin has only a few "probably inconsequential" differences from strain to strain.

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