Botulism: new drug buys time.

Botulism: New drug buys time

Scientists have found that a little-used drug may prove useful in emergency treatment of the most potent of four human-botulism toxins--type A. The treatment has been identified by researchers with the Army Medical Research Institute of Infectious Diseases at Ft. Detrick in Frederick, Md. This drug, a variant of one used in treating myasthenia gravis, enhances the release of the neurotransmitter acetylcholine. Botulism toxins interfere with acetylcholine release.

In studies involving mice given lethal doses of this bacterial toxin, hourly treatment with 34-diaminopyridine (DAP) prolonged survival--sometimes almost doubling or tripling the survival period compared with that of poisoned animals receiving no drug, according to a report in the June 30 TOXICOLOGY AND APPLIED PHARMACOLOGY. However, 34-DAP is not a cure, stresses Lynn S. Siegel, one of the researchers. Though it slowed the progressive paralysis that characterizes the disease, treated animals ultimately died of toxin-induced respiratory failure, generally within 15 hours. As a result, she says, 3,4-DAP is best viewed as a way of buying time to get a patient access to preferred therapy--such as treatment with botulism antibodies or respiratory intensive care.

At least as important as finding this potential temporary treatment, says Siegel, is what the research suggests about the toxins. Clostridium botulina have been classified into seven types, based on the particular neurotoxin--types A through G--that each makes. "The dogma for people involved in botulism research has been that all seven types of toxin act by the same pharmacological mechanism," Siegel says. However, the finding that 3,4-DAP works against only one of the toxins affecting humans "indicates that the toxins are indeed different and have a different mechanism of action."