Experimental drug may block radiation damage

William Atkins
Sunday, 13 April 2008 21:24

Science - Health

The U.S. Department of Defense (DoD) is especially interested in the applicability of the drug to possible nuclear attacks by terrorists.

Because of this use for biodefense, the DoD and other similar government agencies are funding the research by Gudkov.

In fact, Gudkov has founded the Cleveland, Biolab, Inc. to further develop the drug for possible introduction in the marketplace if it is found to be effective in humans and is approved for sale.

According to the Associated Press article “Drug Experiment Blocks Radiation Damage” by Lauran Neergaard, Dr. Richard Kolesnick (Memorial Sloan-Kettering Cancer Center, not associated with the study) stated, "For many years, the radiation oncology community has tried to develop radioprotectants. 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."

The result of the researcher’s work is published in the April 11, 2008 issue of the journal Science. The title of the article is “An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models.”

Its authors are: Lyudmila G. Burdelya, Vadim I. Krivokrysenko, Thomas C. Tallant, Evguenia Strom, Anatoly S. Gleiberman, Damodar Gupta, Oleg V. Kurnasov, Farrel L. Fort, Andrei L. Osterman, Joseph A. DiDonato, Elena Feinstein, and Andrei V. Gudkov.

The abstract to their paper states, “The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates a signaling mechanism used by tumor cells to suppress apoptosis can protect healthy cells from the harmful effects of radiation.”

“We studied CBLB502, a polypeptide drug derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR5) and activates nuclear factor– B signaling. A single injection of CBLB502 before lethal total-body irradiation protected mice from both gastrointestinal and hematopoietic acute radiation syndromes and resulted in improved survival.”

“CBLB502 injected after irradiation also enhanced survival, but at lower radiation doses. It is noteworthy that the drug did not decrease tumor radiosensitivity in mouse models. CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.”