Precision medicine for sodium channelopathy-related autism and epilepsy

Morgan Robinson; Kyle Wettschurack; Manasi S Halurkar; Xiaoling Chen; Zaiyang Zhang; Jingliang Zhang; Yang Yang

doi:10.1016/j.molmed.2025.09.007

Precision medicine for sodium channelopathy-related autism and epilepsy

Trends Mol Med. 2025 Oct 28:S1471-4914(25)00216-3. doi: 10.1016/j.molmed.2025.09.007. Online ahead of print.

Authors

Morgan Robinson¹, Kyle Wettschurack², Manasi S Halurkar², Xiaoling Chen², Zaiyang Zhang², Jingliang Zhang², Yang Yang³

Affiliations

¹ Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA; Department of Chemical Engineering, College of Engineering, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA.
² Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA.
³ Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA. Electronic address: yangyang@purdue.edu.

PMID: 41162233
DOI: 10.1016/j.molmed.2025.09.007

Abstract

Precision medicines for monogenic brain disorders are rapidly advancing. Voltage-gated sodium channel (VGSC) genes are the leading monogenic cause of severe epilepsy and profound autism spectrum disorder (ASD), most notably SCN1A, SCN2A, SCN3A, and SCN8A. Recent advances in animal and human induced pluripotent stem cell (hiPSC) disease models provide a powerful platform for advancing precision medicines. Thanks to the genomic revolution, many gene therapies are in preclinical studies and clinical trials for VGSC-related diseases, including viral vector gene replacement, clustered regularly interspaced short palindromic repeats (CRISPR) base editing, prime editing, and genetic modulation strategies including antisense oligonucleotides, engineered tRNAs, and CRISPR activation/interference (CRISPRa/i). This review highlights the latest advances in disease modeling and next-generation therapeutic development to advance precision medicine for VGSC-related brain disorders.

Keywords: Dravet syndrome; developmental and epileptic encephalopathy; neurodevelopmental disorders; precision medicine; translational neuroscience.

Publication types

Review