Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Curr Neurol Neurosci Rep. 2012 Aug;12(4):410-8. doi: 10.1007/s11910-012-0276-5.
New epilepsy treatments are needed that not only inhibit seizures symptomatically (antiseizure) but also prevent the development of epilepsy (antiepileptogenic). The mammalian target of rapamycin (mTOR) pathway may mediate mechanisms of epileptogenesis and serve as a rational therapeutic target. mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex. The mTOR pathway is also implicated in epileptogenesis in animal models of acquired epilepsy and infantile spasms, although the effects of mTOR inhibitors are variable depending on the specific conditions and model. Furthermore, beneficial effects on seizures are lost when treatment is withdrawn, suggesting that mTOR inhibitors are "epileptostatic" in only stalling epilepsy progression during treatment. Clinical studies of rapamycin in human epilepsy are limited, but suggest that mTOR inhibitors at least have antiseizure effects in tuberous sclerosis patients. Further studies are needed to assess the full potential of mTOR inhibitors for epilepsy treatment.
需要新的癫痫治疗方法，不仅要对症抑制癫痫发作（抗癫痫），还要预防癫痫的发展（抗癫痫发生）。雷帕霉素靶蛋白（mTOR）途径可能介导癫痫发生的机制，并作为合理的治疗靶点。mTOR 抑制剂在结节性硬化症等遗传性疾病的动物模型中具有抗癫痫发生和抗癫痫作用。mTOR 途径也与获得性癫痫和婴儿痉挛的动物模型中的癫痫发生有关，尽管 mTOR 抑制剂的作用因具体情况和模型而异。此外，当停止治疗时，对癫痫发作的有益影响会消失，这表明 mTOR 抑制剂在治疗过程中只是“癫痫稳定”，只能延缓癫痫进展。雷帕霉素在人类癫痫中的临床研究有限，但表明 mTOR 抑制剂至少在结节性硬化症患者中具有抗癫痫作用。需要进一步研究来评估 mTOR 抑制剂在癫痫治疗中的全部潜力。
