New Antidote to Botulism: Drug neutralizes toxin in
mouse tests
Nathan Seppa
An experimental drug disables deadly botulism toxin
much better than current treatment does, researchers
report. They also suggest that the drug could be
mass-produced and stockpiled as a deterrent to the use
of botulism toxin, or botulin, as a weapon.
Scientists in recent years have identified antibodies
that people and animals make when exposed to botulin or
a botulism vaccine. The researchers reporting the new
finding fashioned their drug from three antibodies—two
from mice and one from a person—that bind well to the
toxin. None knocks it out alone, but two thwart it
somewhat, and all three working in concert neutralize
botulin, the researchers report in an upcoming
Proceedings of the National Academy of Sciences.
When injected into mice, the triple antidote protects
the animals even when they're exposed to amounts of the
toxin far beyond those that are normally lethal.
The precise mechanism by which the antibodies disable
botulin isn't known, says report coauthor
Leonard A.
Smith, a molecular biologist at the U.S. Army Medical
Research Institute of Infectious Diseases at Fort Detrick in Frederick, Md.
Smith and his colleagues used one of seven known
types of botulin in their study. With their strategy,
the scientists will probably succeed in making antidotes
against all six other types, predicts Bal Ram Singh, a
biochemist at the University of Massachusetts in
Dartmouth. "It's a good approach," he says.
The Centers for Disease Control and Prevention in
Atlanta lists botulism as one of the six most dangerous
bioterrorism threats. By one estimate, a single gram of
botulin dispersed evenly in a form that could be inhaled
would kill 1 million people. Having a powerful
antidote—once it's been tested in volunteers—will make a
difference, Singh says. "This will be a deterrent," he
notes.
Mass vaccination against botulism appears unlikely
since cases are rare and the current vaccine is scarce.
Each year, only about 100 people in the United States
get botulism poisoning, usually from contaminated food.
With treatment and hospitalization, almost all of them
recover.
Doctors now treat patients with antibodies purified
from the blood of people or horses vaccinated against
botulism toxin, but the new drug is up to 90 times as
potent. Smith and his colleagues are considering growing
it in yeast or rice as a way to mass-produce the new
drug inexpensively.
References:
Nowakowski, A., . . . L. Smith, et
al. In press. Potent neutralization of botulinum
neurotoxin by recombinant oligoclonal antibody.
Proceedings of the National Academy of Sciences.
Further Readings:
Arnon, S.S., et al. 2001.
Botulinum toxin as a biological weapon: Medical and
public health management. Journal of the American
Medical Association 285(Feb. 28):1059-1070.
Available at http://jama.ama-assn.org/issues/v285n8/ffull/jst00017.html.
Shapiro, R.L., C. Hatheway, and D.L.
Swerdlow. 1998. Botulism in the United States: A
clinical and epidemiologic review. Annals of Internal
Medicine 129(Aug. 1):221-228. Available at http://www.acponline.org/journals/annals/01aug98/botulism.htm.
Shapiro, R.L., et al 1997.
Botulism surveillance and emergency response: A public
health strategy for a global challenge. Journal of
the American Medical Association 278(Aug.
6):433-435. Available at http://jama.ama-assn.org/issues/v278n5/ffull/jco71053.html#top.
Vangelova, L. 1995. Botulinum toxin:
A poison that can heal. FDA Consumer
29(December). Available at http://www.fda.gov/fdac/features/095_bot.html.
Additional information about
Botulinum toxin is available at http://www.hopkins-biodefense.org/pages/agents/agentbotox.html.
Sources:
Bal Ram Singh
University of
Massachusetts, Dartmouth
Department of Chemistry and
Biochemistry
285 Old Westport Road
Dartmouth, MA
02747
Leonard A. Smith
USAMRIID
1425
Porter Street
Frederick, MD 21702-5011
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