Despite the wide availability of potassium iodine to mitigate ingestion exposure to radioactive iodine in the air, food or beverages, there is still no magic medicine to give to people who have been—or will be—exposed to high levels of direct radiation.

But years before the disaster at the Fukushima Daiichi nuclear power plant in Japan, the U.S. government had started lobbing millions of dollars at contracts to speed the development of drugs to combat dangerous doses of ionizing radiation.

The military is "very interested in drugs that you can give before radiation or very shortly after," says Mark Whitnall, program advisor for Radiation Countermeasures at the U.S. Department of Defense's Armed Forces Radiobiology Research Institute (AFRRI), which has spearheaded recent development efforts.

Aside from radiation sickness caused by nuclear attacks or accidents, anti-radiation drugs could have applications for people receiving radiation therapy for cancer, those with weakened immune systems or even for astronauts undertaking long-distance space travel.

Lethal exposures
Depending on the type of exposure, radiation can pose a wide range of health risks. Acute radiation syndrome—often called radiation sickness—is different from health effects related to contact with airborne or foodborne radioactive isotopes (including iodine 131, strontium 90 or plutonium), which are linked to more long-term issues, such as cancer.

People exposed to intense radiation emitted directly from a source such as a nuclear reactor core or weapon, as has occurred with some workers addressing the crisis at the stricken Fukushima power plant in Japan, can suffer from severe infection and gastrointestinal damage (in addition to skin burns, hair loss and other symptoms), which can lead to death within days or months.

Radiation exposure also damages bone marrow, reducing the body's supply of white blood cells and platelets. This renders people more prone to infection as well as uncontrolled bleeding. At extreme levels, it can also harm the lining of the stomach and central nervous system.

Available treatments have leaned on antibiotics to stave off infection, along with blood transfusions to replace white blood cells and platelets.

Another drug that's already out there, a granulocyte colony-stimulating factor (G-CSF) called filgrastim (sold as Neupogen), incites the bone marrow to make more white blood cells. It is indicated for cancer patients whose counts have dropped as a result of radiation treatment and has been noted as a possible treatment for a nuclear power plant radiation emergency, according to the U.S. Centers for Disease Control and Prevention. It does not, however, address the risk of excess bleeding, Whitnall says, noting that, "a loss of platelets [clotting bodies] is really a major cause of death after radiation."

So researchers have been trying to develop drugs that could target blood loss as well and radiation's other effects on the body—both before and after exposure. A prophylactic "radio-protector" for first-responders and military personnel whose work puts them in harms way would be particularly desirable.

But for many people who could unwittingly be caught up in a nuclear accident or attack, "there's a need for a mitigating agent that can be given as long as possible after the event of radiation," says Andrei Gudkov, chief scientific officer of Cleveland BioLabs a company that is currently testing one anti-radiation drug. Their drug, called CBLB502, seems to protect primates for some 48 hours after radiation exposure.

Another drug that is in the works, Ex-RAD (made by Onconova Therapeutics) has been shown to protect mice from long-term damage caused by direct radiation if given either pre- or post-exposure. They hope to make it effective if given up to 24 hours before exposure. Animal studies suggest that it can have a protective effect for exposures even weeks after a dose.

A different type of therapy, CLT-008 (made by Cellerant Therapeutics), is cell-based and administered intravenously; it promises a different type of treatment to boost white blood cells. In animal studies it was effective given as long as three to five days after radiation exposure. Although it would require more substantial medical facilities, it might be a follow-up treatment for those who were able to receive first-line meds. "You could actually triage the people and then appropriately administer this product," says Ram Mandalam, president of Cellerant. Whitnall describes it as "a bridging therapy that will allow the patient to survive for awhile, while his own immune system and blood-forming system can recover."

Ascertaining effectiveness
As tough as it is to develop these drugs, testing them can be even trickier. They can only be systematically checked for safety—not effectiveness—in people. "We can only evaluate in healthy volunteers because we cannot expose people to radiation," explains Manoj Maniar, senior vice president of product development at Onconova, which makes Ex-RAD.

Because companies cannot go around irradiating human subjects, the U.S. Food and Drug Administration allows these sorts of drugs to be tested for efficacy in two animal models—usually mice and monkeys—and for safety alone in healthy people.

So far, the human safety trials have been small: CBLB502 has been tested in about 150 people in the U.S., Ex-RAD in fewer than 100 subjects. "The results were extremely encouraging," Maniar says of the initial human Ex-RAD safety studies. "We did not see any drug-related adverse events in the trial."

With such a small pipeline to work with, Whitnall and his group try to do due diligence in assessing compounds early in the development phase. Researchers must "look for toxicity pretty early to make sure there's no show-stopper," he notes.

But the safety trials will need to be considerably larger before the drugs can be considered for approval. And as part of the modified approval process, regulators also "want to understand the mechanism of injury very well," along with how the drug itself is working, Whitnall says.

Although some of the specifics might still need to be parsed out for the FDA, researchers can already explain the basics. CBLB502 helps to trigger the release of cytokines and chemokines—involved in intracellular communication—which boosts bone marrow and gastrointestinal tract regeneration. Ex-RAD also works via intracellular communication, repairing damaged DNA and preventing cell death (apoptosis).

Disaster-ready
Despite the possible applications, millions of research dollars from the government, and fast-track status from the FDA, drugs to keep people from dying after intense radiation exposure still face additional hurdles before they are ready to distribute in the event of the next nuclear emergency.

7 Comments

1. 1. Pugsley 10:57 PM 4/4/11

   It's wonderful that in a few decades the priviledged classes will get some good remedies for radioactive poisoning, however at this stage of things ordinary people will have to use natural radio-protectors if there's nothing better available. This article is from way back in 1997, go to the 3rd page, 1st column.

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2. 2. Pugsley 10:58 PM 4/4/11

   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469917/pdf/envhper00331-0094.pdf

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3. 3. Homeopathy 11:46 PM 4/4/11

   http://www.prlog.org/11417424-natural-treatment-for-radiation-exposure-what-you-need-to-know-to-not-get-sick.html
   
   Radioactive water found leaking into sea from pat at Japan nuclear plant. This radiation is now showing up in the rain water falling into the United States and Canada at levels 1000% of normal. This can be devastating to say the least to all humankind! The effects of radiation sickness and poisoning include cancer, genetic and reproductive damage, hormonal damage, and thyroid blockage (that's why they want you to take potassium iodine, another dangerous toxin) but I wouldn't. There are much safer substances like <a href="http://thehealingfrequency.com/zeolite/">Zeolite</a>.

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4. 4. Rhythman 03:24 AM 4/5/11

   Yes, genetic defects in future generations are usually left out of the discussions we're hearing these days.
   Of course this is going to be very expensive as would be the chelation therapies and others for attempting internal de-contamination.
   
   The worst outcome would be giving the impression that it's OK to produce more nuclear materials on a continuing basis as well as making nuclear war more 'thinkable'.
   
   

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5. 5. okwhen 07:45 AM 4/5/11

   One thing that always strikes me quite odd when reading any article on radiation exposure is no mention of how dangerous the effects of air born radioactive particles are. I worked in nuclear power plants and the training I received remains with me to this day. Of all the radiation exposure the worst is inhaled. That is unless the dose is enough to cause death. The reason inhaling radiation is the worst, there is no way of removing it other than a bilateral transplant. Once the radiation is inhaled it continues giving off harmful radiation until the life span expires. I do not believe any of the newly discovered or experimental drugs cover that period of duration.

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6. 6. fernaguil 10:21 PM 4/5/11

   I am so concern about the tons of radioactive water that Tepco drop to Pacific Sea, biological marine life is in danger, our Pacific Sea food is contaminated now with Cesium 137 30 years of decay Cesium 135 2.3 million years, cesium 134 2 years...-All the fish of Pacific will be contaminated in different levels, what can we do?.

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7. 7. jloch 09:28 PM 4/8/11

   Cancer is caused mutations to DNA. Ionizing radiation causes reactive oxygen species to form, which subsequently react with DNA to mutate it. Antioxidants neutralize this process. Many fruits and vegetables as well as supplements such as N-acetyl cysteine act as antioxidants. It seems like supplementing one's diet with high amounts of fruits and vegetables would be a natural (and cheap and widely available) way to combat some of the radiation-induced cellular damage. Why is no one talking about this? It's simple common sense. Japanese people should be pouring all the fruit juices and fresh vegetables into their bodies they can get their hands on. It's not like they're going to suffer side effects from eating fruits and vegetables. This strategy could only help and do no harm, unlike experimental drugs that haven't been tested in humans. I don't disagree with some of the strategies outlined above, but ingesting large amounts of antioxidants before or during exposure to radiation should be encouraged, not ignored.

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