Prevention of Temporal Lobe Epilepsy

颞叶癫痫的预防

• 批准号: 8551776
• 负责人: James O. McNamara
• 金额: $ 42.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8551776
• 关键词: Address; Adult; Amygdaloid structure; Animal Model; Anticonvulsants; Biological Markers; Brain; Child; Childhood; Clinical; Data; Development; Disease; Epidemiology; Epilepsy; Epileptogenesis; Experimental Designs; Febrile Convulsions; Fever; Generalized Epilepsy; Genetic; Goals; Grant; Hippocampus (Brain); Human; Hyperthermia; Image; Impaired cognition; Individual; Induced Hyperthermia; Infusion procedures; Injury; Institution; Intervention; Ipsilateral; Kainic Acid; Laboratories; Life; Liquid substance; Magnetic Resonance Imaging; Measures; Methods; Modeling; Modification; Molecular; Mus; Neurobiology; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pilot Projects; Population; Prevention; Preventive; Proteins; Rattus; Refractory; Research; Research Infrastructure; Research Personnel; Sclerosis; Seizures; Series; Serum; Signal Transduction; Status Epilepticus; Structure; Study models; Syndrome; Temporal Lobe Epilepsy; Testing; United States National Institutes of Health; Universities; Validation; base; clinical phenotype; cohort; cytokine; data acquisition; high risk; hippocampal atrophy; medical schools; meetings; mouse model; nervous system disorder; pre-clinical; prevent; public health relevance; pup; small molecule; working group

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.

描述（由申请人提供）：癫痫是一种严重的常见神经系统疾病，估计全世界有 1% 的人口受到影响，而颞叶癫痫 (TLE) 是成人中最严重和难治性的癫痫。没有有效的预防方法。临床观察以及对不同动物模型的研究表明，儿童时期的发热性癫痫持续状态 (FSE) 可能会导致以后的 TLE。因此，FSE 相关 TLE 是一种可以检查预防性治疗的癫痫综合征。我们的总体目标是确定 (a) 候选化合物和 FSE 后 TLE 临床预防试验的备份，以及 (b) 应针对的高风险个体的预测生物标志物 进行干预。为了实现这些目标，我们组建了一个临床前研究人员团队，重点研究癫痫发生机制。该规划拨款的目标是： 1) 创建一个紧凑的行政基础设施，以促进我们的核心团队、NIH 以及我们的学术和制药公司顾问之间的互动，并吸引更多的研究人员参与其开发的项目； 2) 开展试点研究，旨在识别动物模型中与临床表型相符的生物标志物。我们的目的是提交一份后续申请，建立一个没有疾病改变和预防围墙的癫痫中心 (CWW)。以下目标将实现 CWW 规划阶段的目标。目标 1 建立一个行政结构，负责监督和协调规划拨款期间的活动，并为无墙中心做好准备。目标 2 确定与延长 FSE 后的成像生物标志物密切相关的细胞因子生物液分析物谱。目标 3 建立一个多机构团队，协调高热或 KA 诱发癫痫发作后 MRI 成像的实用性和可预测性研究。 目标 4 通过研究 FEBSTAT 队列，直接检查这些生物标志物对人类癫痫、晚期海马损伤和认知障碍的预测能力。