Recent advances and current status of gene therapy for epilepsy.

Background: Epilepsy is a common neurological disorder with complex pathogenic mechanisms, and refractory epilepsy often lacks effective treatments. Gene therapy is a promising therapeutic option, with various preclinical experiments achieving positive results, some of which have progressed to clinical studies.

Data sources: This narrative review was conducted by searching for papers published in PubMed/MEDLINE with the following single and/or combination keywords: epilepsy, children, neurodevelopmental disorders, genetics, gene therapy, vectors, transgenes, receptors, ion channels, micro RNAs (miRNAs), clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9 (CRISPR/Cas9), expression regulation, optogenetics, chemical genetics, mitochondrial epilepsy, challenges, ethics, and disease models.

Results: Currently, gene therapy research in epilepsy primarily focuses on symptoms attenuation mediated by viral vectors such as adeno-associated virus and other types. Advances in gene therapy technologies, such as CRISPR/Cas9, have provided a new direction for epilepsy treatment. However, the clinical application still faces several challenges, including issues related to vectors, models, expression controllability, and ethical considerations.

Conclusions: Here, we summarize the relevant research and clinical advances in gene therapy for epilepsy and outline the challenges facing its clinical application. In addition to the shortcomings inherent in gene therapy components, the reconfiguration of excitatory and inhibitory properties in epilepsy treatment is a delicate process. On-demand, cell-autonomous treatments and multidisciplinary collaborations may be crucial in addressing these issues. Understanding gene therapy for epilepsy will help clinicians gain a clearer perception of the research progress and challenges, guiding the design of future clinical protocols and research decisions.