Genetic Signatures in Human Temporal Lobe Epilespy

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Epilepsy affects about 2.5 million people in the USA and 40 million worldwide. Of this population 40% are patients with Temporal Lobe Epilepsy (TLE). In approximately 45% of those with TLE, seizures cannot be well controlled by currently available medications. Epilepsy surgery helps a proportion of these patients, but remains a costly procedure with a risk of morbidity. The mechanisms underlying the maintenance of seizures in medically refractory TLE remain unknown. There is at present no fundamental understanding of the genes that increase risk for TLE. The studies proposed in this application seek to apply a powerful new technology, microarray analysis of gene expression, to hippocampal tissue from patients with TLE. Ribonucleic Acid from the dentate area and Ammon's horn regions separated by microdissection of the hippocampus, surgically removed for the treatment of TLE will be microarrayed using the Affymetrix human GeneChip U133. These studies aim to define the molecular profiles of TLE syndromes, identify candidate genes related to human TLE and define markers of epileptogenicity. The studies also aim to develop a set(s) of "outcome classifier genes" for epilepsy surgery. The importance of such studies have been identified in the "benchmarks" for epilepsy research by the NINCDS conference "Curing Epilepsy: Focus on the Future". These studies will provide the essential foundation for a major new and rapid series of future studies to uncover the mechanisms that initiate and maintain seizures in this disorder, and identify new targets for drug development.