Lentiviral potassium channel expression to treat focal neocortical epilepsy

在英国，癫痫影响着大约30万人，其中约10万人对现有药物没有反应。一种特别严重的耐药癫痫（局灶性新皮质癫痫）通常发生在癫痫发作时，癫痫发作是由大脑中一小块异常组织引起的。因为大脑的其余部分通常是完整的，所以应该有可能改变异常区域神经元的兴奋性，以阻止癫痫发作或在癫痫发作时终止癫痫发作。我们已经验证了局灶性新皮质癫痫的实验模型，并做了大量的基础工作，使用修饰的病毒来改变神经元中单个基因的表达。我们建议降低癫痫发作灶神经元的兴奋性，或者增强抑制性神经元的兴奋性。我们的工作将建立在初步数据的基础上，这些数据是我们通过研究由编码离子通道的基因突变引起的罕见神经系统疾病的后果而获得的，离子通道是单个神经元电信号基础的蛋白质。

Epilepsy affects approximately 300,000 people in the UK, of whom about 100,000 do not respond to available medication. An especially severe form of drug-resistant epilepsy (focal neocortical epilepsy) often occurs when seizures arise from a small area of abnormal tissue in the brain. Because the rest of the brain is often intact, it should be possible to alter the excitability of neurons in the abnormal area to stop seizures arising or to terminate them when they occur. We have validated an experimental model of focal neocortical epilepsy and have done much ground-work to use modified viruses to change the expression of individual genes in neurons. We propose to reduce the excitability of neurons in the seizure focus, or alternatively to enhance the excitability of inhibitory neurons. Our work will build on preliminary data that we have obtained by studying the consequences of rare neurological disease caused by mutations of genes that encode ion channels, proteins that underlie the electrical signalling of individual neurons.