Snowball Albert, Schorge Stephanie
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
FEBS Lett. 2015 Jun 22;589(14):1620-34. doi: 10.1016/j.febslet.2015.05.004. Epub 2015 May 12.
Chronic pain and epilepsy together affect hundreds of millions of people worldwide. While traditional pharmacotherapy provides essential relief to the majority of patients, a large proportion remains resistant, and surgical intervention is only possible for a select few. As both disorders are characterised by neuronal hyperexcitability, manipulating the expression of the most direct modulators of excitability - ion channels - represents an attractive common treatment strategy. A number of viral gene therapy approaches have been explored to achieve this. These range from the up- or down-regulation of channels that control excitability endogenously, to the delivery of exogenous channels that permit manipulation of excitability via optical or chemical means. In this review we highlight the key experimental successes of each approach and discuss the challenges facing their clinical translation.
慢性疼痛和癫痫共同影响着全球数亿人。虽然传统药物疗法能为大多数患者提供必要的缓解，但仍有很大一部分患者对此耐药，且只有少数患者能够接受手术干预。由于这两种疾病都以神经元过度兴奋为特征，操纵兴奋性最直接的调节因子——离子通道——的表达代表了一种有吸引力的通用治疗策略。人们已经探索了多种病毒基因治疗方法来实现这一点。这些方法包括上调或下调内源性控制兴奋性的通道，以及递送允许通过光学或化学手段操纵兴奋性的外源性通道。在这篇综述中，我们强调了每种方法的关键实验成功之处，并讨论了它们临床转化所面临的挑战。
