Recent advances and current status of gene therapy for epilepsy  

作　　者：Ao-Jje Cai Kai Gao Fan Zhangg Yu-Wu Jiang 

机构地区：[1]Department of Pediatrics,Peking University First Hospital,Beijing,China [2]Department of Pediatrics,The First Affiliated Hospital of Zhengzhou University,Henan Province,Zhengzhou,450052,China [3]Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases,Beijing,China [4]Children Epilepsy Center,Peking University First Hospital,Beijing,China [5]Key Laboratory for Neuroscience,Ministry of Education/National Health and Family Planning Commission,Peking University,Beijing,China [6]Center of Epilepsy,Beijing Institute for Brain Disorders,Beijing,China

出　　处：《World Journal of Pediatrics》2024年第11期1115-1137,共23页世界儿科杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(grant number:U22A20339,82171435,81971211,81601131);by the National Key Research and Development Program of China(grant number:2020YFA0804000);by Key Project of Clinical Medicine Research of National Clinical Research Center for Child Health and Disorders,Children’s Hospital of Chongqing Medical University(grant number:NCRCCHD-2021-KP-02);by Beijing Natural Science Foundation(grant number:7212109);by the capital health research and development of special(2020-1-4071);by the Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases(grant number:BZ0317);by the Fundamental Research Funds for the Central Universities(grant number:BMU2017JI002,BMU2018XY006,PKU2017LCX06);by the Henan Province science and technology joint construction project(LHGJ20230224).

摘　　要：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.

关 键 词：CHALLENGES CRISPR EPILEPSY Gene therapy STRATEGY 

分 类 号：R742.1[医药卫生—神经病学与精神病学]