{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:29Z","timestamp":1791928889728,"version":"4.3.4"},"reference-count":98,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU\u2014Ministero della Salute PNRR M6\/C2\u2014Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["PNRR-MR1-2022-12376642"],"award-info":[{"award-number":["PNRR-MR1-2022-12376642"]}]},{"DOI":"10.13039\/100031478","name":"NEXTGENERATIONEU","doi-asserted-by":"crossref","award":["DN.1553 11.10.2022"],"award-info":[{"award-number":["DN.1553 11.10.2022"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Variants 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.<\/jats:p>","DOI":"10.3390\/ijms27010032","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:27:16Z","timestamp":1766154436000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9250-5610","authenticated-orcid":false,"given":"Giorgia","family":"Dinoi","sequence":"first","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-316X","authenticated-orcid":false,"given":"Ileana","family":"Canfora","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"D\u2019Agnano","sequence":"additional","affiliation":[{"name":"Children Epilepsy and EEG Center, San Paolo Hospital, ASL Bari, 70132 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-8490","authenticated-orcid":false,"given":"Brigida","family":"Boccanegra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5125","authenticated-orcid":false,"given":"Elena","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-7341","authenticated-orcid":false,"given":"Annamaria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-7577","authenticated-orcid":false,"given":"Antonella","family":"Liantonio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-573X","authenticated-orcid":false,"given":"Vittorio","family":"Sciruicchio","sequence":"additional","affiliation":[{"name":"Children Epilepsy and EEG Center, San Paolo Hospital, ASL Bari, 70132 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5350","authenticated-orcid":false,"given":"Paola","family":"Imbrici","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/dmcn.14519","article-title":"Sodium channel epilepsies and neurodevelopmental disorders: From disease mechanisms to clinical application","volume":"62","author":"Brunklaus","year":"2020","journal-title":"Dev. 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