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Anti-radiation Pill May Protect Bone Marrow

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A new drug protects mice from radiation damage to bone marrow, even if taken up to 20 hours after radiation exposure, according to the research team that developed it.

While some current drugs offer some protection from radiation toxicity if ingested in advance, this would be the first “radiomitigant,” able to mitigate bone-marrow damage even when taken after radiation exposure.

Norman Sharpless, MD, led the research team. He’s associate director for translational research at the University of North Carolina Lineberger Comprehensive Cancer Center and an associate professor of medicine and genetics at UNC’s School of Medicine. Both institutions are in Chapel Hill.

A School of Medicine news release quoted Dr. Sharpless as saying:

We believe this study is really exciting. We have identified a simple, nontoxic pill that decreases radiation toxicity even when given after radiation exposure. We believe this approach could be of use in humans who are accidentally or intentionally exposed to lethal doses of radiation.

Oral treatment of mice with the new drug inhibited enzymes involved in cell division. That caused certain groups of bone-marrow cells to temporarily stop dividing, a state that the researchers called “pharmacological quiescence,” or PQ. Previous research has shown that cells that are not dividing are resistant to DNA damage from radiation.

The pill worked when taken anytime from immediately before to 20 hours after a normally lethal dose of radiation. PQ protected all normal blood cells, including platelets, red cells, and white cells.

The active agents are selective inhibitors of certain cellular enzymes, called CDK4 and CDK6. Related drugs have been used in treating human cancer patients, and the CDK4 and CDK6 inhibitors are currently being tested in humans. The drugs have little toxicity, can be given in pill form, and are chemically stable.

Dr. Sharpless said PQ might also be used to treat cancer patients. Not only radiation therapy but also some chemotherapy drugs destroy bone marrow by damaging DNA, so PQ might mitigate side effects of both therapies. The researchers addressed the question of whether PQ might also shield cancer cells from radiation therapy or chemotherapy. They found that at least some kinds of cancer were not protected.

Results of the study were published this week in The Journal of Clinical Investigation. UNC has filed patents related to the discoveries and licensed them to a company called G-Zero Therapeutics, which was cofounded in 2007 by Dr. Sharpless and colleagues in Boston and San Francisco.

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