Scientists in the US have developed a drug that protected laboratory mice and monkeys from radiation damage and may one day be used to protect people from the side effects of radiation used in medical procedures such as cancer treatments, and even the effects of nuclear weapons.
A study describing the laboratory findings is published today, 11th April, in the early online issue of Science and is the work of investigators from the Roswell Park Cancer Institute and Cleveland BioLabs, Inc, both in Buffalo, New York; plus the Lerner Research Institute at the Cleveland Clinic in Ohio, and the Burnham Institute for Medical Research in La Jolla, California.
Exposure to radiation causes cells to commit suicide by triggering programmed cell death or apoptosis. However, tumour cells have a way of stopping apoptosis, which is why cancer cells proliferate.
Cleveland BioLabs developed an experimental drug called CBLB502 to activate the signalling mechanism used by tumour cells to suppress apoptosis to see if it could protect healthy cells from radiation harm.
CBLB502 is a polypeptide derived from the whip like tails of the Salmonella bacterium and it binds to a cell receptor called TLR5 to trigger appropriate apoptosis-suppressing signal.
For this study, the scientists gave laboratory mice a single injection of CBLB502 and then exposed them to a lethal total body dose of radiation.
The drug protected the mice against the effects of radiation on organs of the digestive tract and in blood cell producing bone marrow (protected against “gastrointestinal and hematopoietic acute radiation syndromes”) and improved their survival.
Other mice that were injected after being irradiated also survived longer, but only at lower doses of radiation.
Similar effects were demonstrated in rhesus monkeys, with 90 per cent of lethally irradiated monkeys surviving after three weeks compared with 20 per cent of the controls.
The scientists concluded that:
“TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.”
Last week, on 3rd April, the US Department of Defense awarded Cleveland BioLabs an 8.9 million dollar preliminary contract to develop CBLB502 as a “Medical Radiation Countermeasure to treat radiation injury following exposure to radiation from nuclear or radiological weapons.”
The company is developing another series of drugs called CBLB600, which stimulate the immune system. These could be used with CBLB502 to protect against radiation damage (which also affects the immune system) or on its own to reduce the side effects of chemotherapy.
They are also exploring the use of CBLB600 as a way to produce stem cells after discovering that the compound increases numbers of hematopoietic stem cells (HSC) in both the bone marrow and peripheral blood.
“An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models.”
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.
Science 11 April 2008, Vol. 320. no. 5873, pp. 226 – 230.
DOI: 10.1126/science.1154986.
Sources: Journal Abstract, Cleveland BioLabs.
Written by: Catharine Paddock, PhD