Prevention of Temporal Lobe Epilepsy

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DESCRIPTION (provided by applicant): Epilepsy is a serious common neurological disorder, afflicting an estimated 1% of the population worldwide, and temporal lobe epilepsy (TLE) is the most severe and refractory epilepsy in adults. There is no effective prevention. Clinical observations as well as studies of diverse animal models underlie the idea that febrile status epilepticus (FSE) in childhood can cause TLE later in life. Therefore, FSE-related TLE is one epilepsy syndrome for which preventive therapies could be examined. Our overarching goals are to identify (a) a candidate compound and a backup for a clinical prevention trial of TLE following FSE, and (b) predictive biomarker(s) for individuals at high risk that should be targeted for intervention. To achieve these goals, we have assembled a team of preclinical investigators with research focus on mechanisms of epileptogenesis. The objectives of this planning grant are: 1) To create a compact administrative infrastructure that will promote interactions among our core team, NIH and our academic and pharmaceutical company consultants as well as draw additional investigators into the project it develops; 2) To conduct pilot studies aimed at identification of biomarkers across animal models aligned with the clinical phenotype. Our intent is to submit a subsequent application for an Epilepsy Center without Walls on Disease Modification and Prevention (CWW). The following Aims will enable the objectives of the planning phase of the CWW. Aim 1 to develop an administrative structure that oversees and coordinates the activities during the planning grant and prepares for a Center without Walls. Aim 2 To identify a cytokine bio fluid analyte profile that correlates strongly with imaging biomarkersafter prolonged FSE. Aim 3 to establish a multi-institutional team to coordinate study of the utiliy and predictability of MRI imaging following induction of seizures induced by hyperthermia or KA. Aim 4 to directly examine the predictability of these biomarkers for epilepsy, late hippocampal injury, and cognitive impairments in humans, by studying the FEBSTAT cohort.