Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA.
Expert Rev Neurother. 2013 Jun;13(6):657-69. doi: 10.1586/ern.13.48.
Present medications for epilepsy have substantial limitations, such as medical intractability in many patients and lack of antiepileptogenic properties to prevent epilepsy. Drugs with novel mechanisms of action are needed to overcome these limitations. The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Preliminary clinical trials suggest that mTOR inhibitors reduce seizures in tuberous sclerosis complex (TSC) patients with intractable epilepsy. Furthermore, mTOR inhibitors have antiepileptogenic properties in preventing epilepsy in animal models of TSC. Besides TSC, accumulating preclinical data suggest that mTOR inhibitors may have antiseizure or antiepileptogenic actions in other types of epilepsy, including infantile spasms, neonatal hypoxic seizures, absence epilepsy and acquired temporal lobe epilepsy following brain injury, but these effects depend on a number of conditions. Future clinical and basic research is needed to establish whether mTOR inhibitors are an effective treatment for epilepsy.
目前的抗癫痫药物存在着诸多局限性，例如许多患者的医学难治性和缺乏预防癫痫的抗癫痫发生特性。因此，需要具有新作用机制的药物来克服这些局限性。mTOR 信号通路已成为治疗癫痫的一个可能的治疗靶点。初步的临床试验表明，mTOR 抑制剂可减少结节性硬化症（TSC）患者的癫痫发作，这些患者的癫痫发作难以治疗。此外，mTOR 抑制剂在预防 TSC 动物模型的癫痫发生方面具有抗癫痫发生的特性。除 TSC 外，越来越多的临床前数据表明，mTOR 抑制剂可能对其他类型的癫痫（包括婴儿痉挛症、新生儿缺氧性癫痫发作、失神性癫痫和脑损伤后的获得性颞叶癫痫）具有抗惊厥或抗癫痫发生作用，但这些作用取决于许多条件。需要进行未来的临床和基础研究，以确定 mTOR 抑制剂是否是一种有效的癫痫治疗方法。
