Pharmacoresistant limbic epilepsy: model validation

耐药边缘癫痫：模型验证

• 批准号: 6831039
• 负责人: EDWARD H BERTRAM
• 金额: $ 20.66万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-02 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831039
• 关键词: anticonvulsants; brain disorder chemotherapy; chronic disease /disorder; disease /disorder model; dosage; electroencephalography; electrostimulus; epilepsy; kainate; laboratory rat; limbic system; method development; model design /development; multidrug resistance; neuropharmacology; nonhuman therapy evaluation; partial seizure; pilocarpine; temporal lobe /cortex disorder; therapy design /development

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通过现有药物得到成功控制，但尽管尝试了多种药物治疗，仍有约三分之一的癫痫发作持续。 这组患者被定义为治疗抵抗，这是最需要更有效治疗的群体。 虽然有迅速扩大的证据表明，在治疗耐药患者的大脑中存在多种可能改变药理学反应特征的变化，但治疗发现过程依赖于在正常动物的大脑中使用急性诱导癫痫发作。 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，这可能是治疗抵抗性癫痫所独有的。 此应用程序是对申请公告的响应，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后持续状态模型中验证药物抗性。 在这个项目的过程中，我们将实现几个目标，将满足本RFA的主要目的。 总的来说，我们将建立一种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式，我们将创建和验证在具有间歇性自发性癫痫发作的慢性啮齿动物癫痫模型中给予治疗剂量的化合物的方法。 该项目将通过建立基线数据和引入新方法来评估新化合物治疗癫痫的治疗潜力，从而实现项目目标。