Genetic Signatures in Human Temporal Lobe Epilespy

描述（由申请人提供）：癫痫影响美国约250万人，全球约4000万人。在这一人群中，40%的患者患有颞叶癫痫（TLE）。在大约45%的TLE患者中，目前可用的药物无法很好地控制癫痫发作。癫痫手术有助于这些患者的一部分，但仍然是一个昂贵的程序与发病率的风险。医学难治性TLE癫痫发作维持的机制尚不清楚。目前还没有对增加TLE风险的基因的基本了解。本申请中提出的研究试图将一种强大的新技术，基因表达的微阵列分析应用于TLE患者的海马组织。通过海马的显微切割分离的齿状区和阿蒙角区的核糖核酸，手术切除用于治疗TLE，将使用Affyphine人基因芯片U133进行微阵列。这些研究的目的是确定TLE综合征的分子特征，识别与人类TLE相关的候选基因，并确定致癫痫性的标志物。这些研究还旨在开发一组用于癫痫手术的“结果分类基因”。这些研究的重要性已经被NINCDS会议“治愈癫痫：关注未来”确定为癫痫研究的“基准”。这些研究将为未来一系列重大的、新的、快速的研究提供重要基础，以揭示这种疾病中引发和维持癫痫发作的机制，并确定药物开发的新靶点。

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.