Xu Cenglin, Gong Yiwei, Wang Yi, Chen Zhong
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Pharmacol Ther. 2022 May;233:108026. doi: 10.1016/j.pharmthera.2021.108026. Epub 2021 Oct 28.
Epilepsy, one of the most severe neurological diseases, is characterized by abrupt recurrent seizures. Despite great progress in the development of antiseizure drugs (ASDs) based on diverse molecular targets, more than one third of epilepsy patients still show resistance to ASDs, a condition termed pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy involves serious challenges. In the past decade, promising advances have been made in the use of interdisciplinary techniques involving biophysics, bioinformatics, biomaterials and biochemistry, which allow more precise prognosis and development of drug target for pharmacoresistant epilepsy. Notably, novel experimental tools such as viral vector gene delivery, optogenetics and chemogenetics have provided a framework for promising approaches to the precise treatment of pharmacoresistant epilepsy. In this review, historical achievements especially recent advances of the past decade in the prognosis and treatment of pharmacoresistant epilepsy from both clinical and laboratory settings are presented and summarized. We propose that the further development of novel experimental tools at cellular or molecular levels with both temporal and spatial precision are necessary to make improve the management and drug development for pharmacoresistant epilepsy in the clinical arena.
癫痫是最严重的神经系统疾病之一,其特征是突然反复发作。尽管基于多种分子靶点的抗癫痫药物(ASD)研发取得了巨大进展,但仍有超过三分之一的癫痫患者对ASD耐药,这种情况被称为药物难治性癫痫。药物难治性癫痫的管理面临严峻挑战。在过去十年中,涉及生物物理学、生物信息学、生物材料和生物化学的跨学科技术应用取得了有前景的进展,这些技术能够为药物难治性癫痫提供更精确的预后评估和药物靶点开发。值得注意的是,诸如病毒载体基因递送、光遗传学和化学遗传学等新型实验工具为药物难治性癫痫的精准治疗提供了有前景的方法框架。在本综述中,我们展示并总结了药物难治性癫痫预后和治疗方面的历史成就,尤其是过去十年临床和实验室环境中的最新进展。我们认为,在细胞或分子水平上进一步开发具有时间和空间精度的新型实验工具,对于改善临床领域药物难治性癫痫的管理和药物开发是必要的。