Potential EEG biomarkers and antiepileptogenic strategies for epilepy in TSC

描述（由申请方提供）：TSC中癫痫的潜在EEG生物标志物和抗癫痫策略目前癫痫的治疗方法主要代表抑制癫痫发作的对症治疗，但尚未证明可预防癫痫或改变疾病进展。近年来，人们对开发疾病修饰或“抗癫痫”疗法产生了极大的兴趣。 多发性硬化症（TSC）是癫痫的常见遗传原因，TSC患者的一个子集可能代表了一个合理的，可行的人群，以抗癫痫治疗方法为目标。首先，由于存在非神经学发现，一些患者在癫痫发作前的年轻时被诊断为TSC：这些发现的存在使得识别这些患者并在癫痫发生的早期阶段开始潜在的抗癫痫治疗是可行的。其次，这些患者将来患癫痫的风险很高。由于这些因素，在症状前阶段启动具有潜在副作用的治疗可能在TSC患者中是合理的。最后，在TSC的病理生理学中鉴定mTOR通路表明mTOR抑制剂在TSC中可能具有抗癫痫特性，但可能存在显著的风险和副作用。因此，在TSC患者中启动抗癫痫药物试验之前，获得进一步的证据以优化选择标准和治疗模式，以最大限度地提高mTOR抑制剂的疗效并最大限度地减少副作用，以及建立临床前和临床研究中心网络将是有益的。在这项P20资助申请中，我们建议进行临床前和临床研究，为潜在的抗癫痫药物试验建立最佳参数。临床前核心将旨在确定最佳的雷帕霉素治疗模式，保持抗癫痫疗效，但最大限度地减少副作用的风险。临床核心旨在确定婴儿期的EEG是否是一种可靠的生物标志物，以识别将发生癫痫的TSC患者，从而确定抗癫痫药物试验的合适候选人。我们还将为TSC癫痫中心建立基础设施，这将促进此类临床试验。

DESCRIPTION (provided by applicant): Potential EEG biomarkers and antiepileptogenic strategies for epilepsy in TSC Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease progression. In recent years, there has been tremendous interest in developing disease-modifying or "antiepileptogenic" therapies. Tuberous Sclerosis Complex (TSC) is a common genetic cause of epilepsy and a subset of TSC patients may represent a rational, feasible population to target an antiepileptogenic treatment approach. First of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due to the presence of non-neurological findings: The presence of these findings makes it feasible to identify these patients and initiate a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these patients are at high risk for developing epilepsy in the future. Because of these factors initiating a therapy with potential side effects in a presymptomatic stage can likely be justified in TSC patients. Finally, the identification of the mTOR pathway in the pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties in TSC but there may be significant risks and side effects. Therefore, before initiating an antiepileptogenic drug trial in TSC patients, it would be beneficial to obtain further evidence to optimize the selection criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR inhibitors, as well as establish a network of preclinical and clinical sites. n this P20 grant application we propose to conduct pre-clinical and clinical studies that establish optimal parameters for a potential antiepileptogenic drug trial. The preclinical core will aim to determine the optimal rapamycin treatment paradigms that maintain antiepileptogenic efficacy but minimize risks of side effects. The clinical core aims to determine whether EEGs during infancy are a reliable biomarker to identify TSC patients that will develop epilepsy and thus appropriate candidates for an antiepileptogenic drug trial. We will also establish the infrastructure for a TSC Epilepsy Center Without Walls, which will facilitate such clinical trials.