If a one-kiloton nuclear device exploded in New York City, it would kill or sicken millions of people because there are no effective and non-toxic treatments for victims of acute radiation syndrome. But a new Pentagon-funded drug currently proceeding through human trials potentially could help save many of those lives.
Cleveland BioLabs Inc. of Buffalo, N.Y., has developed a radiation countermeasure, called Protectan CBLB502. When given as a single injection, as many as 80 percent of those exposed to total body irradiation could survive.
In experiments with monkeys, scientists could not find traces of radiation poisoning in more than half of the test animals after 40 days had elapsed from the time of irradiation and administration of the drug.
Protectan CBLB502 works by temporarily suppressing cell death so that the body can make the necessary repairs, says Michael Fonstein, president and chief executive officer of the company, whose studies of tumor protection mechanisms led to the discovery of the drug.
When healthy tissues and cancerous tumors are exposed to radiation, cells in both cases die. But they perish for different reasons. When tumors are hit by radiation, their cells cannot find and repair the damage, so they go into remission and die, he explains. Healthy tissues can tolerate high doses of radiation. But some tissues, including hair follicles, elements of the intestinal tract and bone marrow, are hypersensitive to radiation and are more susceptible to a phenomenon called apoptosis, or suicidal death of cells. In these tissues, cells die off before healing can happen.
If given time to repair, scientists thought, the cells might survive.
Compounds in Protectan CBLB502 not only slow cell death, but they also appear to speed up revival by inducing molecules to destroy free radicals and by causing the proliferation of regenerating cytokines, or the proteins that serve as messengers between cells.
“There’s a lot of hope and excitement about the possibility of having a drug like this,” says John Parker, a science advisor to the lab. “502 is clearly distinct from anything that’s in the arsenal today.”
Radiation antidotes in the nation’s stockpile target specific isotopes. Potassium iodine, for example, counters the effects of exposure to Iodine-131, an isotope that was released following the 1986 nuclear reactor accident at Chernobyl. When taken, potassium iodine travels to the thyroid to block the radioactive iodine and allow its excretion. But it would not protect other parts of the body from the isotope, nor would it be effective against other radioactive substances.
Protectan CBLB502, on the other hand, is agnostic to radioisotopes because it targets the damaged tissue cells themselves. The antidote, which can be administered effectively 48 hours and up to 72 hours after irradiation, would be valuable to the U.S. stockpile to counter surprise attacks, company officials say.
But the drug also could be taken as a preventative measure.
“We’ve demonstrated through scientific studies of both mice and primates that you can give 502 before the fact and then be exposed, and it’s protective,” Parker says.
If the Pentagon sends troops into a future conflict in which exposure to a nuclear weapon is likely, then it could administer the drug to military personnel to prevent adverse effects, says Parker, a retired major general who commanded the Army Medical Research and Materiel Command at Fort Detrick, Md., from 1998 to 2002.
The drug’s development has been funded privately and also publicly through federal government contracts totaling $23 million from the Defense Department, the National Institutes of Health and the Department of Health and Human Services.
Fonstein says the price of the product has not been finalized. His company invested internal development dollars in the drug, and that money must be recouped. However, “we have a very efficient manufacturing process that would allow us to keep costs reasonably low,” he says.
The company recently finished the first of a two-step process of human trials. “We have determined that there were no serious adverse side effects of the drug,” says Rachel Levine, director of corporate development and communications. The trial also allowed scientists to determine the drug’s maximum safe dosage.
The next phase involves a larger human safety study to test one dose in a few hundred healthy volunteers. It would be completed in about a year, which would keep the firm on track to submit its biologic license application filing to the Food and Drug Administration in late 2010.