Epilepsy: Molecular Pathogenesis and Emerging Therapies

Epilepsy is a prevalent and often severe neurological disorder with significant economic and societal impacts. Despite adequate trials with two or more antiseizure medications (ASMs), approximately one-third of patients continue to experience drug-resistant epilepsy. Surgery remains the most effective treatment for patients with drug-resistant focal epilepsy, yet it may be underutilized. Given the unsatisfactory clinical outcomes, it is imperative to investigate the molecular pathogenesis of epilepsy and to develop novel therapeutic strategies. This review systematically outlines the advances in understanding the etiology and molecular pathogenesis of epilepsy. These advances have identified diverse therapeutic targets, stimulating the development of emerging therapies, including novel ASM, minimally invasive surgery, neurostimulation, focused ultrasound, nanomedicine, gamma-aminobutyric acid (GABA)ergic cell therapy, and gene therapy. Additionally, the review comprehensively evaluates emerging therapies for epilepsy from different perspectives by integrating findings from both preclinical and clinical studies. These innovative approaches offer the potential for long-term seizure control. A great deal of future research is still needed to overcome current shortcomings. This work provides a cohesive framework that bridges molecular mechanisms with therapeutic applications. Such efforts may provide novel ideas and optimizing approaches in the field, ultimately advancing the precision and effectiveness of epilepsy treatments in the future.