期刊
EXPERT REVIEW OF NEUROTHERAPEUTICS
卷 18, 期 3, 页码 185-201出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14737175.2018.1428562
关键词
Epilepsy; epileptogenesis; everolimus; malformations; mTOR inhibitors; mTORopathies; rapamycin; tuberous sclerosis complex
资金
- EPISTOP [602391]
- Stichting Michelle
Introduction. The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for proper neural network development, and it is involved in epileptogenesis triggered by both genetic or acquired factors.Areas covered. The robust mTOR signaling deregulation observed in a large spectrum of epileptogenic developmental pathologies, such as focal cortical dysplasias and tuberous sclerosis complex (TSC), has been linked to germline and somatic mutations in mTOR pathway regulatory genes, increasing the spectrum of mTORopathies'. The significant advances in the field of TSC allowed for the validation of emerging hypotheses on the mechanisms of epileptogenesis and the identification of potential new targets of therapy. Recently, a double-blind phase III randomized clinical trial on patients with TSC related epilepsy, demonstrated that adjunctive treatment with mTOR inhibition is effective and safe in reducing focal drug resistant seizures.Expert commentary. mTOR signaling dysregulation represents a common pathogenic mechanism in a subset of malformations of cortical development, sharing histopathological and clinical features, including epilepsy, autism, and intellectual disability. EXIST-3 trial provided the first evaluation of the optimal dosage, conferring a higher chance of reducing seizure frequency and severity, with adverse events being similar to what observed with lower dosages.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据