Could common antihistamines become antidote to deadly chemical agent?
In March 2019, the FBI entered an Oklahoma City apartment and found massive amounts of dangerous chemicals. Among the chemicals was Phosgene oxime, or CX, one of the deadliest chemical agents ever manufactured.
CX, categorized with blistering agents like mustard gas, is a nettle agent or urticant, a variety of chemical that causes serious allergic reactions that rapidly incapacitate and kill a person, but there’s no known antidote, according to Neera Tewari-Singh, assistant professor of pharmacology and toxicology in the College of Osteopathic Medicine at Michigan State University.
With a $1.4 million grant from the National Institutes of Health Countermeasures Against Chemical Threats, or the NIH-CounterACT program, Tewari-Singh is working on an antidote. CounterACT’s goal is to integrate research and technological advances in science and medicine to improve medical response to chemical emergencies, whether they are acts of terrorism or industrial disasters.
Created in 1929 by German chemists and stockpiled during World War II, CX was developed as a potential deadly chemical warfare agent, but its use in battlefield is not reported, Tewari-Singh said.
“What adds to CX’s deadliness is that it’s easily manufactured and one of the least studied of all chemical threat agents,” she said. “Our study will provide the first major insight into its toxicity and effects on the body.”
In her ongoing research, Tewari-Singh has found that CX could target the body’s mast cells, which are associated with allergy and inflammation-related issues. Because of this, she will further investigate if mast cells are key players and targets in CX toxicity, and test whether epinephrine, the medicine in “EpiPen” that treats severe allergic reactions, or other antihistamines could be effective antidotes to CX.
Because it’s dangerous, CX can’t be stored or studied at MSU; it can only be tested at government-approved facilities. With that in mind, Tewari-Singh is developing an antidote using mice that are exposed to CX by trained personnel using appropriate biosafety, biocontainment and security measures at MRIGlobal, a research institute in Kansas City, Missouri. After exposure to CX at MRIGlobal, mice tissue is then sent to Tewari-Singh’s lab at MSU for testing. CX degrades fast so humans are not at risk from the exposed mice tissue.
If she can find an antidote to CX, Tewari-Singh said it may possibly counteract other chemical agents she has been studying as well, which is important since the nation is increasingly at risk.
“Technological advances have increased the risk of occupational and accidental exposure to toxic chemical agents in addition to their potential use in warfare and terrorism,” Tewari-Singh said. “Effective and targeted medical interventions currently don’t exist for most chemical threat agents; so in order to save lives and enhance the nation’s medical response capabilities in an event of a chemical disaster, it’s critically important that they are developed.”