Institute for Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Department of Medical Genetics and Clinical Neurophysiology, Krasnoyarsk State Medical University, Partizana Zheleznyaka 1, Krasnoyarsk 660022, Russia.
Int J Mol Sci. 2024 Nov 11;25(22):12081. doi: 10.3390/ijms252212081.
Epilepsy is a brain disorder characterized by a persistent predisposition to epileptic seizures. With various etiologies of epilepsy, a significant proportion of patients develop pharmacoresistance to antiepileptic drugs, which necessitates the search for new therapeutic methods, in particular, using gene therapy. This review discusses the use of adeno-associated viral (AAV) vectors in gene therapy for epilepsy, emphasizing their advantages, such as high efficiency of neuronal tissue transduction and low immunogenicity/cytotoxicity. AAV vectors provide the possibility of personalized therapy due to the diversity of serotypes and genomic constructs, which allows for increasing the specificity and effectiveness of treatment. Promising orientations include the modulation of the expression of neuropeptides, ion channels, transcription, and neurotrophic factors, as well as the use of antisense oligonucleotides to regulate seizure activity, which can reduce the severity of epileptic disorders. This review summarizes the current advances in the use of AAV vectors for the treatment of epilepsy of various etiologies, demonstrating the significant potential of AAV vectors for the development of personalized and more effective approaches to reducing seizure activity and improving patient prognosis.
癫痫是一种以持续存在的癫痫发作易感性为特征的脑部疾病。由于癫痫的病因多种多样,相当一部分患者对抗癫痫药物产生耐药性,因此需要寻找新的治疗方法,特别是使用基因治疗。本综述讨论了腺相关病毒(AAV)载体在癫痫基因治疗中的应用,强调了其优势,如神经元组织转导效率高,免疫原性/细胞毒性低。AAV 载体由于血清型和基因组构建体的多样性,提供了个性化治疗的可能性,这使得治疗的特异性和有效性得以提高。有前途的方向包括调节神经肽、离子通道、转录和神经营养因子的表达,以及使用反义寡核苷酸来调节癫痫发作活动,这可以减轻癫痫疾病的严重程度。本综述总结了 AAV 载体在治疗各种病因癫痫中的应用的最新进展,展示了 AAV 载体在开发个性化和更有效的方法来减少癫痫发作活动和改善患者预后方面的巨大潜力。