The National Institute of Neurological Disorders and Stroke (NINDS) has awarded Emory neuroscientists a three-year, $2 million grant to develop new anti-inflammatory drugs for the prevention of comorbidities related to epilepsy.
Epilepsy affects more than one in 100 people, and often is associated with cognitive deficits such as memory impairment. Several types of anti-epileptic drugs are available, but none has been proven to prevent the progression of epilepsy or ensuing comorbidities after initial seizure episodes.
Thota Ganesh, PhD, and Ray Dingledine, PhD, have been investigating the potential for EP2 antagonists, which inhibit signals from inflammatory prostaglandins, to prevent the development of comorbidities associated with epilepsy. Ganesh says EP2 antagonists act as a sort of “fire extinguisher,” interrupting the chain of events occurring in the brain in response to an initial injury by seizures.
“In animal models, we have shown EP2 receptor activation is responsible for blood-brain barrier leakage and much of the inflammatory reaction, neuronal injury and cognitive deficits that follow seizure-provoked induction of the enzyme cyclooxygenase 2,” Ganesh says.
The researchers will conduct further studies to identify EP2 antagonist candidate compounds for eventual study in human clinical trials. They hope to develop the first preventative treatment for cognitive deficits related to epilepsy through this research.
“In the broader population of people with epilepsy, especially the common form of epilepsy located in the temporal lobe, memory problems are quite widespread. Solving the cognitive problems will be a major advance in the epilepsy field,” Dingledine says.
Ganesh is associate professor, and Dingledine professor, both in the Department of Pharmacology and Chemical Biology at Emory University School of Medicine.
The grant from NINDS is part of a program created by the National Institutes of Health’s Blueprint for Neuroscience Research Initiative, and is designed to support the development of new neurotherapeutics. It comes with milestone requirements each year, as well as supplemental funding for contract research organizations to perform preclinical pharmacology work.
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