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 A single dose of the experimental drug protected both mice and monkeys from what should have been lethal doses of radiation, researchers report in Friday's edition of the journal Science. A study to see if the compound is safe in people could begin as early as this summer.
It's still early-stage research, and other efforts to create radiation protectants haven't yet panned out. But specialists are closely watching the work
-- and the government is helping to fund it -- because it's a new approach to protecting the body's most radiation-sensitive tissues from being blasted.
"It has important implications for radiation exposure," said Dr. David Kirsch, a Duke University radiation oncologist who wasn't involved in the drug research.
Radiation is a powerful tool to destroy cancer cells. But certain healthy tissues are especially sensitive to it, too, particularly the bone marrow and gastrointestinal tract. That vulnerability can limit how much radiation physicians are able to give cancer patients.
And when it comes to radiation emergencies, such as the Chernobyl accident, full-body exposure to high doses can cause an extremely lethal "GI syndrome" that has no treatment.
It turns out that radiation doesn't kill healthy cells in the same way that it kills cancer cells. Instead, bone marrow and GI cells overreact to what should be reparable damage and commit suicide, through a well-known process called apoptosis, explained Andrei Gudkov of the Roswell Park Cancer Institute, who led development of the drug code-named CBLB502.
Learning that was the "eureka" moment, Gudkov said. Apoptosis is the body's way of stopping defective cells, with damaged genes, from spreading. Tumors grow because cancer cells block apoptosis in various ways, including by activating a normally dormant cell-signaling pathway called "nuclear factor-KappaB" or NFKB.
Gudkov's team decided to try activating that same pathway in healthy tissue, to see if it could keep radiation-blasted cells from triggering their suicide program.
"We imitated a tumor trick," is how Gudkov puts it.
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The team knew that flagellin, a protein from normal gut bacteria, can wake up NFKB. So they created a drug based on that natural protein.
In a series of experiments, they injected the drug into mice and
rhesus monkeys anywhere from 15 minutes to an hour before exposing
the animals to lethal doses of full-body radiation. The drug
dramatically improved the animals' survival, protecting against both
bone marrow and GI destruction, with no obvious side effects.
The drug also improved survival when given to mice an hour after
fairly high radiation doses, although not the very highest.
A final experiment showed the drug didn't block radiation from
treating the tumors of the mice even as it protected their healthy
tissue.
Gudkov founded a company called Cleveland Biolabs Inc. that is
working to bring the drug to market -- both for use in cancer
radiotherapy and for biodefense. The Defense Department and other
government agencies are helping to fund the research.
"For many years, the radiation oncology community has tried to
develop radioprotectants" based on different biology, said Dr.
Richard Kolesnick of Memorial Sloan-Kettering Cancer Center, who has
long researched radiation's effects. "This new information on the
mechanisms of tissue damage to the GI tract has resulted in a
potentially important new drug to prevent this lethal GI syndrome
after a radiation accident or potential terrorist attack."
Duke's Kirsch agreed that the animal experiments suggest the drug
has potential for radiation emergencies. But he stressed that a
cancer role is less clear, because cancer patients' biggest trouble
comes with late-stage radiation effects, the cumulative buildup of
damage. "That's what's dose-limiting," he said.
[Associated
Press; By LAURAN NEERGAARD]
Copyright 2008 The Associated
Press. All rights reserved. This material may not be published,
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