A new $17 million research center dedicated to identifying medical countermeasures for neurotoxic chemicals that cause seizures in humans has been established by the U.S. National Institutes of Health at the University of California, Davis. The research also is expected to yield findings that could improve medical treatment for people with seizure disorders.
The new UC Davis CounterACT Center of Excellence is part of the NIH Countermeasures Against Chemical Threats Research Network. Professor Pamela Lein, a developmental neurobiologist and neurotoxicologist in the UC Davis School of Veterinary Medicine, will direct the new center.
“Neurotoxic chemicals have the sobering potential to cause massive disabling and even lethal seizures among a civilian population,” Lein said. “It’s imperative that new and improved antidotes be developed so that emergency responders and medical professionals have the tools to not only protect themselves when responding to an emergency involving these chemicals, but also to minimize the neurological damage from such chemicals in individuals who survive the exposure, whether those chemicals are released intentionally or accidentally.”
The research program will focus on a group of chemicals known as organophosphates and on TETS, which stands for tetramethylenedisulfotetramine. TETS is a powerful neurotoxin once used as a rat poison but now banned in most parts of the world.
Organophosphates, many used in pesticides like parathion, can cause seizures by inhibiting the enzyme that normally would regulate muscle contractions and critical pathways of communication in the brain. Inhibition of this enzyme causes overstimulation or over-excitation of the downstream cell in the circuit, and this increased excitability triggers seizures.
Although the mechanism by which TETS induces potentially lethal seizures is not fully understood, the chemical, in effect, releases the biochemical “brake” that would normally control electrical signals between brain cells.
Lein said that the chemicals studied in the center’s research projects will be used in very small amounts in experimental models. The studies will be conducted in existing campus laboratories.
The research program is expected to produce additional benefits including a better understanding of the biological mechanisms that cause seizures, new neuroimaging techniques and biomarkers for monitoring neurological damage following chemically induced seizures, and novel approaches for medically controlling seizures in people who have epilepsy.
The new center, which is funded for five years, consists of three research projects. One of the projects, to be led by Lein, will focus on developing drugs and treatment procedures that will minimize brain damage in patients who survive seizures.
Another project, led by Michael Rogawski, a professor of neurology in the UC Davis School of Medicine, will focus on identifying improved treatments for preventing seizures. Rogawski, an authority on drugs for treating epileptic seizures, also serves as associate director of the new center.
A third project will be led by Isaac Pessah, professor and chair of the Department of Molecular Biosciences in the UC Davis School of Veterinary Medicine. The project will focus on developing new rapid-throughput tests and high-resolution imaging techniques to be used in screening compounds for potential anticonvulsant and anti-inflammatory activity. Pessah is an expert on calcium signaling in neurons, which is thought to be involved in neuronal damage triggered by organophosphates and TETS.
Other center researchers from UC Davis include Bruce Hammock, a toxicologist and professor of entomology; Heike Wulff, a medicinal chemist and associate professor of pharmacology in the School of Medicine; Danh Nguyen, a statistics expert in the UC Davis Clinical and Translational Science Center; and Bora Inceoglu, a biochemist and pharmacologist in the Department of Entomology.
More information on the NIH Countermeasures Against Chemical Threats Research Network is available at: http://www.ninds.nih.gov/research/counterterrorism/counterACT_home.htm.