Chemet, a drug developed by Ovation Pharmaceuticals Inc. of Deerfield, Ill., to treat the symptoms of radiation exposure, wasn't getting much attention until last November. But that month, a rare radioactive isotope was used to murder former Russian intelligence agent Alexander Litvinenko, and a week later, Ovation got a call from the National Institute of Allergy and Infectious Diseases: Could the company brief the agency on Chemet?
Ovation is one of a few U.S. drug companies and laboratories that are attracting new attention because of Mr. Litvinenko's death in London from poisoning by polonium-210. In the case of Ovation, the company hasn't received federal funding but thinks its chances have dramatically improved.
The federal government's interest precedes Mr. Litvinenko's murder, and is linked with the Sept. 11, 2001, terrorist attacks on the U.S. In 2003, the Bush administration launched Project Bioshield, a federal program to obtain drugs against nuclear, biological and chemical agents. One of the program's aims is to prepare for a possible attack on the U.S. by terrorists using a "dirty bomb" -- a conventional explosive laced with a lethal chemical, biological or nuclear agent.
Last fall, the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and the Pentagon separately offered funding for research into promising radiation-injury treatments. The institute is looking for remedies for civilians, while the Pentagon is seeking to prolong the lives of soldiers irradiated by nuclear weapons.
Now, pharmaceutical companies are giving notice that drugs they have developed, or are developing, for cancer and other diseases can also be used for exposure to radioactive elements, including possibly polonium-210. Most must be taken within hours of exposure to be effective.
British authorities haven't completed their investigation of Mr. Litvinenko's murder, but say that his killers may have slipped the isotope of polonium-210 into his drink or food Nov. 1, when his first symptoms appeared. He died Nov. 23 in a London hospital after weeks of agony.
Radioactive elements attack the body by damaging the DNA in blood cells. The cells stop dividing and die, and the body ends up short of the blood cells it needs to survive. Chemet (pronounced KEM-et) works by accelerating the evacuation of heavy-metal isotopes from the body. It works by binding with the isotope and moving it from the bone marrow -- essential to produce blood cells -- to the kidney, says Jason Bradt, Ovation's executive director of medical affairs. The movement away from the marrow "increases survivability," he says. Kidney damage can be dealt with later.
Cleveland Biolabs Inc. takes a different approach with its drug Protectan. The Cleveland-based company developed the drug as a cancer treatment, but in November it said it was responding to a Department of Defense announcement seeking a radiation-treatment drug. Andrei Gudkov, the company's chief scientific officer, says that he was inundated with questions after Mr. Litvinenko became an international news story.
Protectan works by preventing cells from self-destructing, thus giving "them a time window to repair the damage," Mr. Gudkov says. "You give the cells the metaphorical equivalent of antidepressants."
Mr. Gudkov says he can't be sure that Protectan, meant to work against gamma rays, will be effective against polonium-210, which emits another kind of energy called alpha particles. Gamma rays pass through solid objects; Alpha particles travel only a short distance, can't penetrate the skin, and only cause damage if ingested or inhaled. Inside the body, alpha particles bombard and punch holes in organs. "I tell them we can't say [Protectan] will work with alpha particles" until it's tested on a nonhuman primate, says Mr. Gudkov.
A third possible antidote for polonium-210 is being developed by Hollis-Eden Pharmaceuticals Inc. of San Diego and the Pentagon. The drug, Neumune, treats radiation by promoting the growth of bone marrow. But a drug like Neumune starts working only after an isotope like polonium-210 is expelled from the body, says Dwight Stickney, Hollis-Eaton's vice president for medical affairs.
So one idea would be to combine drugs. One like Chemet, for instance, would remove the isotope from a victim's body, or isolate it in a lethally nonthreatening place like the kidney; a drug like Protectan could stop the cells from committing suicide; and one like Neumune could promote production of more blood cells.
"There could be multiple cocktails that could have a synergistic benefit," says Ovation's Mr. Bradt. <<
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