New Drug Strikes Nerve Agent

(Released 21 August 2018) Fort Belvoir, VA – Used in many attacks such as the 1995 Tokyo subway incident, multiple Syrian chemical strikes and several assassinations, horrifying nerve agent assaults are becoming more common for both civilians and warfighters. Although medical countermeasures exist to sustain life after organophosphate (OP) nerve agent exposure, the risk of brain damage, behavioral and neurological disorders due to prolonged seizures persist. The Defense Threat Reduction Agency’s Chemical and Biological Technologies Department has handed over development of Tezampanel, a new drug to counteract the long-term impacts of nerve agent poisoning to the Biomedical Advanced Research and Development Authority (BARDA), enabling warfighters to recover. 

OP agents act by inhibiting acetylcholinesterase activity. Without pharmacological intervention, the ensuing seizure activity can have serious effects. Currently, treatment for OP exposure is a cocktail of drugs administered immediately after exposure. Benzodiazepines are also used to suppress the seizures; however, treatment is temporary. 

The new development stems from research originally conducted by Maria Braga, Ph.D., at the Uniformed Services University of the Health Sciences, which was supported by DTRA and the National Institute of Health’s CounterACT program. Braga’s research demonstrated that blocking the GluR5KR receptor in the brain after nerve agent exposure protected against behavioral deficits and brain damage. 

GluR5KR antagonists, despite their relatively slow time in suppressing nerve agent-induced seizures, dramatically reduces the total duration of seizures. They also increase protection against neuronal loss and irreversible degeneration in a number of brain regions that play a central role in emotional and cognitive behavior. 

This fundamental research led to the development of LY293558, a receptor antagonist that is an effective anticonvulsant and neuroprotectant. Building upon this research, the U.S. Department of Health and Human Services prompted the development of Tezampanel and subsequent research support through BARDA. In non-clinical, non-good laboratory practices trials Tezampanel is shown to effectively reduce seizures related to nerve agent poisoning, even when the drug was given after a significant delay. 

DTRA’s priority is to deliver timely, innovative solutions to our warfighters. In efforts to restore readiness to build a more lethal force, enabling them to rebound from a nerve agent attack is critical. 

Alison E. Director-Myska, Ph.D.
Email: alison.e.myska.civ@mail.mil

Maria F. Braga, D.D.S., Ph.D.
Email: maria.braga@usuhs.edu

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