Published On July 27, 2022
In March, when Russian forces seized Europe’s largest nuclear power plant, people across the continent flocked to pharmacies seeking potassium iodine tablets. When taken before exposure to high-dose radiation—say, from an explosion at a nuclear power plant—such tablets can deliver iodine to the thyroid gland. This can prevent inhaled or ingested radioactive iodine from settling in the thyroid and triggering cancer down the road.
Thyroid cancer is only one of many pathologies, including other cancers, that can arise from exposure to nuclear radiation. Within minutes, people exposed to heavy radiation doses can develop acute radiation syndrome (ARS), with symptoms that can quickly escalate from nausea and vomiting to life-threatening complications in the bone marrow and gut.
For many of these conditions, the only treatments are imperfect or unavailable. But Russia’s war on Ukraine—and fears that the conflict might bring nuclear power plant incidents or even nuclear warfare—has galvanized efforts in the United States and Europe to increase supplies of existing radiation medications, improve current treatments and develop new therapies to prepare for the worst. “Every day, I hope that the work we do is never needed,” says Andrea DiCarlo-Cohen, the director of the radiation and nuclear countermeasures program at the National Institute of Allergy and Infectious Diseases (NIAID).
The U.S. government has been earnestly funding research into solutions for radiation-related emergencies since 2004, in the wake of the September 11 attacks three years earlier. Those efforts have helped develop four treatments now approved by the Food and Drug Administration for ARS. Those drugs target the blood-cell generating bone marrow, the body system most sensitive to radiation, and three were previously licensed to boost low blood-cell counts in cancer patients. Studies showed they increased survival in non-human primates exposed to high-dose radiation. Now some of the four treatments are stockpiled across the U.S., along with potassium iodide and other protective agents, DiCarlo-Cohen says. In March, the American drugmaker Partner Therapeutics said it was ramping up on supplies of one of the four drugs, Leukine, in Europe.
There’s still no approved drug, however, to treat the gastrointestinal complications of ARS. These involve damage to the gut epithelium, fluid loss and sepsis that can lead to death within weeks, according to Amato Giaccia, a professor emeritus of radiation oncology at Stanford whose research has identified a protein that helps protect against lethal radiation to the gastrointestinal tract.
RxBio, in Tennessee, is one of several companies working to develop treatments for those complications, known as GI-ARS. Its top candidate, Rx100, is related to lysophosphatidic acid (LPA), a natural molecule known to stimulate cell proliferation and survival. Research by University of Tennessee scientists suggests that such LGA analogs, when given within 72 hours of radiation exposure, improve the survival of mice. Importantly, the molecule reduces apoptosis (cell suicide) and boosts the survival of crypt cells of the small intestine, which supply stem cells needed to renew the gut lining. “Rx100 protects that stem cell,” says Shannon McCool, co-founder and president of RxBio, who notes that although some $40 million in federal funding (including from NIAID) has gone into developing the compound, more funding will be need to assess the drug’s effectiveness in larger animals.
Other research targets lung complications of ARS and conditions such as ulceration and scarring of the skin, DiCarlo-Cohen says.
The French company Medesis Pharma, meanwhile, is seeking to improve treatments that could rid the body of ingested or inhaled radioactive particles. Much as supplemental iodine can keep its radioactive counterpart out of the thyroid, the chemicals Prussian blue and calcium DTPA bind to radioactive cesium and plutonium, respectively, and purge them from the body. Yet in their current formulations, both chemicals are unsuitable for mass casualty situations. Treatment with Prussian blue requires many doses of large pills that would be hard for infants or children to swallow, and calcium DTPA typically requires injections.
Medesis has adapted its drug delivery system, which uses special emulsions that can be administered orally or through the lining of the cheek mucosa—to deliver the two chemicals more quickly and effectively, says Marc Bigret, who manages the company’s nuclear products. In unpublished studies in mice, the Medesis formulation of Prussian blue drove down cesium concentrations in heart tissues much more quickly than standard treatments. The next step is to test the drugs for safety in healthy volunteers, Bigret says.
Stanford’s Giaccia cautions, however, that even if the Medesis treatment is found to be safe and effective in people, it would need to be administered before radiation damage to the bone marrow or the GI tract. Moreover, radioactive particles produced by the detonation of nuclear weapons or nuclear accidents can vary and have a range of biological effects, says Bigret, and those could require different kinds of treatments.
Still, with the treatments that have already been approved and dozens more in the pipeline, DiCarlo-Cohen believes government investments into nuclear preparedness are paying off. “We’re in a much better place than we were in 2004,” she says.
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