[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-462295-105":59,"doc-detail-462295-en":122},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":115,"head_meta":117,"extra_data":119,"updated_unix":121},105,"en","from-symptomatic-therapies-to-disease-modifying-approaches-for-neuronal-sodium-channel-disorders-review","From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders - Review","","Neuronal sodium channel gene variants drive a spectrum of neurological disorders, including developmental and epileptic encephalopathies (DEEs), characterized by substantial genetic and phenotypic heterogeneity and frequent drug resistance. Variants may cause loss-, gain-, or mixed-function effects, producing complex genotype–phenotype relationships. Current care is dominated by symptomatic antiseizure polytherapy, where sodium channel blockers are contraindicated in loss-of-function cases but useful in gain-of-function forms. Limited seizure efficacy and insufficient control of developmental impairment motivate disease-modifying strategies. Emerging approaches include antisense oligonucleotides, gene therapy, and selective small molecules, with additional SCN1A-related options such as fenfluramine, stiripentol, and cannabidiol.",{"@graph":69,"@context":114},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/from-symptomatic-therapies-to-disease-modifying-approaches-for-neuronal-sodium-channel-disorders-review/462295/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/from-symptomatic-therapies-to-disease-modifying-approaches-for-neuronal-sodium-channel-disorders-review/462295.png","ImageObject",300,407,{"name":92,"@type":93},"WPS_1786070896","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108],{"name":109,"@type":110,"acceptedAnswer":111},"How do sodium channel blockers differ in effectiveness across variant types?","Question",{"text":112,"@type":113},"Sodium channel blockers are contraindicated in individuals carrying loss-of-function variants, but they can be effective for gain-of-function forms, following a treatment algorithm described for Dravet syndrome.","Answer","https://schema.org",{"og:url":83,"og:type":116,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":118,"canonical":83},"index,follow",{"doc_id":120,"site_id":62},462295,1791163572,{"code":4,"msg":5,"data":123},{"doc_id":120,"user_id":124,"nickname":92,"user_avatar":125,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":131,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":132,"faqs":133,"seo_title":134,"seo_description":67,"update_tm":135,"read_time":31,"preview_page_count":4},549768072016,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nFrom Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders  \nGiorgia Dinoi 1,†, Ileana Canfora 1,†, Daniela D’Agnano 2, Brigida Boccanegra 1, Elena Conte 1, Annamaria De Luca 1, Antonella Liantonio 1, Vittorio Sciruicchio 2 and Paola Imbrici 1, *  \n1 Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, Italy; [giorgia.dinoi@uniba.it](giorgia.dinoi@uniba.it) (G.D.); [ileana.canfora@uniba.it](ileana.canfora@uniba.it) (I.C.); [brigida.boccanegra@uniba.it](brigida.boccanegra@uniba.it) (B.B.);  \n[elena.conte@uniba.it](elena.conte@uniba.it) (E.C.); [annamaria.deluca@uniba.it](annamaria.deluca@uniba.it) (A.D.L.); [antonella.liantonio@uniba.it](antonella.liantonio@uniba.it) (A.L.)  \n2 Children Epilepsy and EEG Center, San Paolo Hospital, ASL Bari, 70132 Bari, Italy;  \n[daniela.dagnano@gmail.com](daniela.dagnano@gmail.com) (D.D.); vittorio.sciruicchio@asl.bari.it (V.S.)  \n* [Correspondence: paola.imbrici@uniba.it](Correspondence: paola.imbrici@uniba.it)[ ](Correspondence: paola.imbrici@uniba.it)† These authors contributed equally to this work.  \nAbstract  \nVariants in neuronal sodium channel genes are responsible for a spectrum of neurological disorders, including developmental and epileptic encephalopathies (DEEs), with considerable genetic and phenotypic heterogeneity and drug resistance. Gene variants can produce loss-, gain-, or mixed-function effects, resulting in complex genotype-phenotype correlations. Current treatments rely mainly on symptomatic polytherapy with antiseizure medications, with sodium channel blockers contraindicated in loss-of-function cases but beneficial in gain-of-function forms. Existing therapies often provide limited benefit or even no seizure control at all and fail to address developmental impairments, highlighting the need for novel approaches. Emerging strategies include antisense oligonucleotides, gene therapy, and selective small-molecule modulators, which have shown antiseizure potential in preclinical models and in initial clinical studies by modulating SCN gene expression and function. Additionally, pharmacological agents such as fenfluramine, stiripentol, and cannabidiol, although not acting directly on sodium channels, represent recognized therapeutic options for SCN1A-related Dravet syndrome. This review summarizes recent advances in approved and investigational treatments for sodium channel-related neurological disorders, highlighting the transition from symptomatic to precision therapies.  \nKeywords: sodium channels; Dravet syndrome; zorevunersen; ETX-101; elsunersen; fenfluramine  \nAcademic Editor: Henry Hing Cheong Lee  \nReceived: 7 November 2025  \nRevised: 11 December 2025  \nAccepted: 16 December 2025  \nPublished: 19 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1. Introduction  \nNeuronal sodium channel genes, SCN1A, SCN2A and SCN8A, have been extensively involved in the pathophysiology of a broad spectrum of neurological disorders, including developmental and epileptic encephalopathy (DEE) in which epilepsy and neurodevelopmental comorbidities coexist [1] . Variants in these genes can result in loss-of-function (LOF), gain-of-function (GOF), or mixed LOF/GOF effects, leading to diverse and complex clinical phenotypes. In the absence of approved therapies that specifically target the underlying molecular defects, the current standard of care of sodium channel-related neuronal disorders mainly relies on polytherapy with antiseizure medications (ASMs), often in combination with drugs aimed at managing associated comorbidities. Importantly, sodium channel blockers (SCBs) are contraindicated in individuals carrying LOF variants but can  \nbe effective in those carrying GOF variants, and a specific treatment algorithm has been establ","cbCaif4WCChpHjGz","https://ap.wps.com/l/cbCaif4WCChpHjGz","pdf",763885,"English","# Abstract\n# Introduction","[{\"question\":\"How do sodium channel blockers differ in effectiveness across variant types?\",\"answer\":\"Sodium channel blockers are contraindicated in individuals carrying loss-of-function variants, but they can be effective for gain-of-function forms, following a treatment algorithm described for Dravet syndrome.\"}]","From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders - Review | PDF",1790763757]