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http://www.jsonline.com/alive/news/apr03/131892.asp

UW, Harvard scientists developing anthrax antidote

By MARILYNN MARCHIONE
mmarchione@journalsentinel.com

Last Updated: April 7, 2003

University of Wisconsin-Madison and Harvard University scientists have achieved a major milestone toward developing an antidote to the deadly anthrax toxin.

While more testing is needed, some say the work might offer the possibility of experimental use of the antidote if another anthrax attack were to occur.

In October 2001, as anthrax was being spread by mail, the researchers discovered a chemical door that the anthrax toxin uses to enter cells and then made a decoy substance to attract the poison to it instead of the cells.

Now they've discovered a second point of entry and made another decoy substance that's even more potent.

"It's about 25-fold better than the first one we had," said John Young, the UW cancer professor who led the research in Madison and will publish its results this week in the Proceedings of the National Academy of Sciences.

The work was part of anti-bioterrorism research that was fast-tracked and funded by the National Institute of Allergy and Infectious Diseases.

Although researchers still need to test the antitoxin decoys in animals and fine-tune them chemically, the decoys might now be a potential emergency treatment.

"This certainly approaches that," said Phillip Baker, who supervises grants for research on a host of biowarfare germs for the infectious diseases institute.

"It could be scaled up quickly," Young agreed. "The hope would be that it would be quick enough to be useful if a need came along like that."

Antibiotics can kill anthrax in the early stages of infection, but symptoms often aren't recognized until after the bacteria have started producing toxin that can rapidly cause death.

"Anthrax toxins have to get into cells to do their damage," so finding out how they do that and blocking it are what's needed in order to develop a successful antidote, Baker explained.

The UW and Harvard researchers now have found two points of entry, or receptors, on cells that allow the toxin to connect and be taken inside the cell. The decoys are free-floating chemical pieces of those receptors. When the toxin attaches to the decoy pieces, it is neutralized and is no longer capable of binding to and getting inside of cells.

"If you have two decoys like this it's better than one" because the anthrax germ might be engineered by a bioterrorist to make a toxin that can evade one mechanism, Baker said.

Test tube experiments have shown the decoys to be effective, and the Harvard team under well-known anthrax researcher John Collier has tested them in rats, although the results have not yet been published.

"All I can say is it shows promising results," Young said.

Similar experiments in people probably could never be done, aside from trying the decoys in an emergency situation, because it would be unethical to deliberately infect people with a deadly germ such as anthrax. But Baker said the lab experiments on human cells suggest encouraging things about their safety.

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