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）：尽管大多数癫痫患者的癫痫发作成功地控制了当前可用的药物，但大约三分之一的三分之一在用多种药物的谨慎治疗中继续癫痫发作。这组患者被定义为耐药性，最需要更有效的疗法的组。尽管有迅速扩大的证据表明，抗治疗患者的大脑可能会改变药理反应特征，但治疗发现过程取决于正常动物的大脑中急性诱发的癫痫发作。这种方法很可能无法解决癫痫发作的机理和潜在的癫痫发作抑制，这可能是耐药性癫痫所特有的。该申请是响应要求公告的请求，以改善这些患者的治疗发现过程。 RFA正在寻求在边缘癫痫的后状态癫痫持续状态中对药物抗性的验证。在这个项目的过程中，我们将实现几个目标，这些目标将达到此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，但是作为满足此目标的步骤，我们将确定使用模型的最有效方法，我们将创建和验证用于管理在某种化合物中进行治疗剂量的方法间歇性自发癫痫发作的癫痫的慢性啮齿动物模型。该项目将通过建立基线数据并引入新方法来评估新型化合物治疗癫痫的治疗潜力，来实现计划目标。