Researchers developing promising antidote to combat deadly anthrax toxin

Posted: Friday, May 31, 2002

SAN FRANCISCO (AP) -- An experimental anthrax antidote has protected rats injected with the bacterium's deadly toxin, researchers found.

University of Texas researchers say they've genetically engineered a mouse protein that offers an anthrax toxin a more attractive docking site than its usual target of healthy blood cells.

''This looks like the most promising antitoxin under development,'' said Dr. Robert Liddington, who studies the poison's atom-by-atom structure at the Burnham Institute in San Diego. ''Certainly, if I had late-stage anthrax I'd pump some of these antibodies into my body.''

The research targets that late stage, which is beyond treatment and often fatal. Anthrax infection can be treated with antibiotics early on, but victims rarely know they are infected until it's too late to save them. By then, the anthrax bacteria have flooded the bloodstream with three deadly toxins, and killing the germs with antibiotics may not help much, because the damage is already done.

So several scientific teams across the country have set their sights on those toxins. The University of Texas research appears to be among the most advanced.

The researchers cautioned that their work, funded by the U.S. Department of Defense since 1997, is still years away from human tests. Still, they said results were promising.

''Although there is a long way to go, our current data makes us very optimistic at this point,'' said Brent Iverson, a University of Texas chemistry professor and co-author of the study published in the June issue of Nature Biotechnology.

In the study, 10 rats were injected with anthrax toxins. Five received the antitoxin and five were untreated. The untreated rats all died within two hours while the treated rats survived the five-hour experiment without displaying any anthrax-related symptoms.

The experiment was limited by ethical protocols to five hours, after which the surviving rats were euthanized.

Anthrax makes three different toxins to poison cells. One is called protective antigen, so named because it is used to make anthrax vaccine. The other two are edema factor and lethal factor.

Protective antigen starts the process by opening a hole in blood cells that lets in edema factor and the even deadlier lethal factor.

The antibody developed by the University of Texas researchers, dubbed 1H, binds with the protective antigen by offering it a more attractive docking surface than the blood cell. The resulting molecule is harmless and eventually clears from the body. The researchers said the 1H antibody can be made quickly, inexpensively and in large quantities.

''Combined with antibiotics, this could represent an effective treatment,'' Iverson said.

Five people died last fall when they were exposed to anthrax-laced letters, and at least 13 others contracted and recovered from either the skin or respiratory form of the disease.

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On the Net:

UT Department of biochemistry: http://www.cm.utexas.edu

Nature Biotechnology: http://www.nature.com/nbt/



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