Posted on 10/23/2001 3:45:12 PM PDT by blam
Scientists herald two potential anthrax cures
October 23 2001 at 05:21PM
New York - Two new findings may someday help doctors deal a one-two punch against inhaled anthrax, targeting not only anthrax bacteria with drugs like Cipro but also the poison those bacteria pump out.
It's the toxin that kills, and by the time a person shows symptoms of inhaled anthrax, antibiotics become less effective because they don't deal with the toxin already produced by the germs.
The new work, announced on Tuesday, may help scientists find ways to neutralise that toxin. Any new medicines, though, would be years away.
In one study, researchers at the University of Wisconsin-Madison and Harvard Medical School said they had identified the chemical foothold that anthrax toxin uses to get inside cells and kill them.
In the other, researchers at The Burnham Institute in La Jolla, California, Harvard and elsewhere said they have determined the detailed structure of a protein that does the toxin's dirty work, a discovery that aids in the search for substances to block it.
The findings, which follow other recent advances toward countering the toxin, will be published online by the journal Nature on Tuesday and printed in its November 8 issue.
Anthrax bacteria create three proteins that team up to make its toxin. One, called protective antigen or PA, latches onto a specific target on the surface of cells and paves the way for the other two proteins to enter.
Until now, nobody has known what the target was.
That "has been sort of a holy grail for anthrax research for quite a while," said Nicholas Duesbery of the Van Andel Research Institute in Grand Rapids, Michigan. Duesbery, an expert on anthrax, wasn't involved in the findings announced in Nature.
The mystery was solved by John Young of the University of Wisconsin-Madison with colleagues there and at Harvard Medical School. They named the cell-surface protein they identified ATR for "anthrax toxin receptor."
They also found that artificial versions of ATR could keep the toxin from killing cells in a laboratory dish, by acting as decoys that diverted the toxin from binding to the cells, Young said.
So treatments with bogus ATR might someday be able to protect people who have been exposed to anthrax, he said in a telephone interview. However, the idea hasn't been tested on animals yet.
The work could also aid the search for substances that interfere more directly with the toxin's attempts to bind ATR, he said.
The other Nature paper reveals the detailed, three-dimensional makeup of "lethal factor," one of the toxin proteins that enters cells. Once it gets inside immune system cells called macrophages, it destroys them, leading to shock and often death for victims of inhaled anthrax.
The discovery of lethal factor's structure should enable scientists to design molecules that can grab onto the protein and disable it, said Robert Liddington of The Burnham Institute, an author of the paper.
"Maybe a year from now we'd actually have some compounds that would work," but they'd still have to go through rigorous testing before they could be used in people, said Liddington.
Scientists had already been able to protect lab animals from the toxin by using other proteins that block its effect, although they caution their efforts are probably years away from useful medicines.
On the Net:
Nature
Does this mean that people with compromised immune systems actually have a better chance for surviving attacks from anthrax's 'lethal factor?'
The Phase I, Phase II, Phase III blind test routine needs to be rethought for anti - toxins!
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