Lentiviral potassium channel expression to treat focal neocortical epilepsy

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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.