[ RadSafe ] Nuclear News - New Drug Protects against Radiation Damage

Evers, William C. WILLIAM.C.EVERS at saic.com
Fri Apr 11 08:25:33 CDT 2008

New Drug Protects against Radiation Damage



A new drug may protect healthy tissue during cancer-killing radiation
treatments or other exposures. Molecular geneticist Andrei Gudkov and
colleagues report in Science this week that they protected mice from the
cell-damaging effects of radiation by injecting them with a compound
that helps cells resist apoptosis, or self-destruction.

Previous studies have found that cancerous cells use nuclear factor
kappa-betaa transcription factor, or protein that turns on or off a
gene's protein-making abilityto outlive normal cells and grow out of
control. But healthy cells in the gut switch on the same transcription
factor when they interact with benign and beneficial bacteria that
reside there. Specifically, the protein flagellin in some of the
microorganisms' whiplike tails (which they use for propulsion) binds
with a receptor on the gut cell and triggers the production of the
transcription factor.

So, in an effort to steel healthy cells against radiation damage,
Gudkov, chairman of the cell stress biology department at Roswell Park
Cancer Institute in Buffalo, N.Y., and his colleagues purified a batch
of flagellin and injected it into mice 30 minutes before exposing them
to lethal doses of radiation.

The injection not only protected the mice's cells but also toughened
them against the effects of free radicals (molecules that can damage DNA
or genetic material inside them) as well as beefed up the animal's
immune systems. Mice without the injection died after the radiation
treatments. "Never before has a single agent been capable of doing all
three things together," Gudkov says.

The researchers then produced a drug called CBLB502 that was designed to
mimic flagellin; it protected 87 percent of the mice from lethal doses
and also safeguarded against free-radical damage. 

They found that the drug only worked if injected within an hour prior to
exposure to high levels of radiation. It also showed some protective
effects if injected after exposure to lower levels. 

The drug did not, however, appear to protect malignant cells from the
radiation treatments designed to kill them. Gudkov says that in addition
to mice, researchers have also tested several dozen human tumor cell
lines and "could not find a single one that benefited" from the drug.

That means the drug, also known as Protectan, could be used, if proved
safe in further testing, to protect patients undergoing bone marrow
transplants or cancer treatments involving radiation. It could also be
given in the event of a nuclear explosion or meltdown. "We envision
people carrying preloaded, self-administrable syringes loaded with the
compound ready for immediate intramuscular injection," Gudkov says. "It
would be given to military and first responders first and, then, why
wouldn't it be available to everybody?"

The U.S. Department of Defense has already signed a contract with
Gudkov's Buffalo-based company, Cleveland BioLabs, Inc., to develop the
drug as a radiation countermeasure. Human safety tests are set to begin
in a few months but will take several years to complete. "Based on
monkey and mice studies, we do not expect any severe side effects,"
Gudkov says.

"The final proof will be empirical testing in large numbers of people.
But we're fairly confident that we are dealing with something pretty


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