Work

Advances in Multidimensional Molecular Mechanisms of Epilepsy and Precision Therapy Strategies

Year: 2026

Type: review

Abstract: INTRODUCTION: Epilepsy is a complex neurological disorder characterized by recurrent seizures. A substantial proportion of patients develop drug-resistant epilepsy (DRE), highlighting the limitations of current therapies and the need to view epilepsy beyond the traditional "channelopathy" hypothesis as a multifactorial network disorder. METHOD: This narrative review synthesizes current evidence on epilepsy pathogenesis, mechanisms of drug resistance, and emerging therapeutic strategies. Relevant studies were identified through literature searches of PubMed and Web of Science, with emphasis on publications from 2018 to 2025 and landmark studies that have shaped current understanding of epileptogenesis, drug-resistant epilepsy, and precision therapy. RESULTS: The pathogenesis of epilepsy converges genetic, neuroinflammatory, and cellular homeostasis pathways. Key drivers include ion channel mutations, glia-mediated neuroinflammation, and dysregulated processes like autophagy and ferroptosis. These contribute to drug resistance and comorbidities, driving a therapeutic shift toward precision and network-modulation strategies, such as gene therapy, targeted pathway modulation, and neuromodulation, with the ultimate goal of achieving disease modification rather than seizure suppression alone. CONCLUSIONS: Integrating multi-omics insights to construct a holistic precision medicine framework, spanning from molecular diagnosis to tailored network therapy, is fundamental for advancing epilepsy treatment. Future efforts must focus on translating this integrated understanding into effective clinical strategies to overcome therapeutic resistance.

Source: CNS Neuroscience & Therapeutics

DOI: 10.1002/cns.71224