Departments of Neurology, Pharmacology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department Biochemistry and Molecular Genetics, School of Medicine, RNA Bioscience Initiative, University of Colorado, PO Box 6511, Aurora, CO, USA.
Neurotherapeutics. 2021 Jul;18(3):1500-1514. doi: 10.1007/s13311-021-01137-z. Epub 2021 Oct 14.
This review summarizes the pathogenic mechanisms that underpin the monogenic epilepsies and discusses the potential of novel precision therapeutics to treat these disorders. Pathogenic mechanisms of epilepsy include recessive (null alleles), haploinsufficiency, imprinting, gain-of-function, and dominant negative effects. Understanding which pathogenic mechanism(s) that underlie each genetic epilepsy is pivotal to design precision therapies that are most likely to be beneficial for the patient. Novel therapeutics discussed include gene therapy, gene editing, antisense oligonucleotides, and protein replacement. Discussions are illustrated and reinforced with examples from the literature.
本文综述了单基因癫痫的发病机制，并讨论了新型精准治疗药物治疗这些疾病的潜力。癫痫的发病机制包括隐性（无效等位基因）、杂合不足、印记、功能获得和显性负性效应。了解每种遗传性癫痫的潜在发病机制对于设计最有可能使患者受益的精准治疗方法至关重要。本文讨论的新型治疗方法包括基因治疗、基因编辑、反义寡核苷酸和蛋白质替代。本文通过文献中的实例进行了说明和强化。
