Terror on a Tokyo subway, 1995; attacks on Syrian civilians, 2013 and 2017; assassinations in an airport in Kuala Lumpur, 2017; attempted assassination in London, 2018. Tremors, foaming at the mouth, seizures, respiratory shutdown, sometimes death. What do these events have in common? Poisoning via a nerve agent – a chemical warfare substance that disrupts communication between the nervous system and muscles and organs.
A major concern for survivors of nerve agent poisoning is the potential for permanent brain damage caused by seizures. Because the brain cannot easily repair such damage, there is a critical need for an antidote that can enter the brain and reverse the early biochemicial effects before harm occurs. Current antidotes, such as 2-PAM, the only FDA-approved reactivator drug in the U.S., cannot do this because it is unable to cross the blood-brain barrier, a layer of cells between the blood and the brain which prevents many chemicals, such as some drugs, from moving from the blood into the brain.
I am a toxicologist in the Center for Environmental Health Sciences in the College of Veterinary Medicine at Mississippi State University (MSU) where I initially worked on toxic responses in laboratory animals to organophosphate insecticides, a widely used class of crop protection chemicals. Organophosphate insecticides have a similar mechanism of action to nerve agents, but are much less toxic and are only approved by the U.S. Environmental Protection Agency for uses that are not going to be harmful to humans or the ecosystem.
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For the past eight years, my team has been developing antidotes that improve survival rates after nerve agent exposure, and we've shown the potential of our new molecules to enter the brain in tests with animals. If approved, these antidotes would give more confidence to both warfighters and civilians that not only could their lives be saved but also their brain function could be preserved.