Pharmacoresistant limbic epilepsy: model validation

耐药边缘癫痫：模型验证

基本信息

批准号：
6931487
负责人：
EDWARD H BERTRAM
金额：
$ 17.62万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-02 至 2007-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Although the majority of the patients with epilepsy have their seizures successfully controlled by currently available medications, approximately one third continue to have seizures in spite therapy attempts with multiple medications. This group of patients is defined as therapy resistant, and it is the group that is in greatest need of more effective therapies. Although there is rapidly expanding evidence that there are multiple changes in the brains of therapy resistant patients that may alter the pharmacological response profile, the therapy discovery process has depended on the use of acutely induced seizures in brains from normal animals. It is very likely that this approach fails to address mechanisms of seizure generation and potential seizure suppression that may be unique to therapy resistant epilepsy. This application is in response to a Request for Applications announcement to improve the therapy discovery process for these patients. The RFA is seeking validation of pharmacoresistance in a post status epilepticus model of limbic epilepsy. In the course of this project we will achieve several goals that will meet the primary purpose of this RFA. Overall we will establish a tool that can be used to test potential new therapies, but as steps in meeting this goal we will determine the most efficient way of using the model, and we will create and validate methods for administering therapeutic doses of compounds in a chronic rodent model of epilepsy with intermittent spontaneous seizures. This project will meet the program goals by establishing baseline data and introducing new methods for evaluating the therapeutic potential of novel compounds for the treatment of epilepsy.

描述（由申请人提供）：虽然大多数癫痫患者通过现有药物成功控制了癫痫发作，但尽管尝试使用多种药物进行治疗，仍有大约三分之一的患者继续癫痫发作。这类患者被定义为治疗抵抗型患者，也是最需要更有效治疗的群体。尽管越来越多的证据表明，治疗抵抗患者的大脑存在多种变化，可能会改变药理反应特征，但治疗发现过程依赖于使用正常动物大脑中的急性癫痫发作。这种方法很可能无法解决癫痫发作产生和潜在癫痫发作抑制的机制，而这可能是治疗抵抗性癫痫所特有的。该申请是对申请公告的回应，旨在改善这些患者的治疗发现过程。 RFA 正在寻求在边缘癫痫的癫痫持续状态模型中验证药物耐药性。在这个项目的过程中，我们将实现几个目标，以满足本 RFA 的主要目的。总体而言，我们将建立一个可用于测试潜在新疗法的工具，但作为实现这一目标的步骤，我们将确定使用该模型的最有效方法，并且我们将创建和验证以治疗剂量施用化合物的方法。具有间歇性自发性癫痫发作的慢性啮齿动物癫痫模型。该项目将通过建立基线数据并引入评估新化合物治疗癫痫的治疗潜力的新方法来实现项目目标。