Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of “therapeutic” genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.

中文翻译：

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使用重组腺相关病毒载体进行神经肽 Y 过表达。


基因疗法可能是对传统抗癫痫药物耐药的癫痫患者的一种有前景的替代治疗方法。在应用基因治疗治疗中枢神经系统疾病的各种方法中，重组腺相关病毒（AAV）载体应用最为广泛。临床前研究使用精选的“治疗”基因注入啮齿动物大脑来纠正癫痫中抑制性和兴奋性传递之间的平衡受损，结果显示癫痫发作显着减少并抑制癫痫发生。特别是，在癫痫实验模型中，神经肽基因（例如甘丙肽和神经肽 Y (NPY)）在特定脑区的转导产生了显着的抗惊厥作用。最近的研究结果表明，通过局部应用重组 AAV 载体，大鼠海马中持久的 NPY 过度表达与癫痫发作的普遍性减少、癫痫发作的延迟以及慢性自发性癫痫发作的强烈减少有关。这些结果为基因疗法作为抗惊厥治疗的功效提供了原理验证证据。需要进行额外的调查来更详细地解决安全问题和可能的副作用。