Specchio Nicola, Pietrafusa Nicola, Perucca Emilio, Cross J Helen
Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy.
Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy.
Epilepsy Behav. 2022 Jun;131(Pt B):107961. doi: 10.1016/j.yebeh.2021.107961. Epub 2021 Apr 16.
Despite the availability of 28 antiseizure medications (ASMs), one-third of people with epilepsy fail to achieve sustained freedom from seizures. Clinical outcome is even poorer for children with developmental and epileptic encephalopathies (DEEs), many of which are due to single-gene mutations. Discovery of causative genes, however, has paved the way to understanding the molecular mechanism underlying these epilepsies, and to the rational application, or development, of precision treatments aimed at correcting the specific functional defects or their consequences. This article provides an overview of current progress toward precision medicine (PM) in the management of monogenic pediatric epilepsies, by focusing on four different scenarios, namely (a) rational selection of ASMs targeting specifically the underlying pathogenetic mechanisms; (b) development of targeted therapies based on novel molecules; (c) use of dietary treatments or food constituents aimed at correcting specific metabolic defects; and (d) repurposing of medications originally approved for other indications. This article is part of the Special Issue "Severe Infantile Epilepsies".
尽管有28种抗癫痫药物（ASMs）可供使用，但三分之一的癫痫患者仍无法实现持续无癫痫发作。发育性和癫痫性脑病（DEEs）患儿的临床结局更差，其中许多是由单基因突变引起的。然而，致病基因的发现为理解这些癫痫的分子机制以及合理应用或开发旨在纠正特定功能缺陷或其后果的精准治疗铺平了道路。本文通过关注四种不同情况，概述了单基因小儿癫痫管理中精准医学（PM）的当前进展，即（a）合理选择专门针对潜在致病机制的抗癫痫药物；（b）基于新型分子开发靶向治疗；（c）使用旨在纠正特定代谢缺陷的饮食治疗或食物成分；以及（d）将最初批准用于其他适应症的药物重新用于治疗。本文是“严重婴儿癫痫”特刊的一部分。
