AutoStopS · GluCl as an epileptic seizure autoregulatory Gene therapeutic approach

GluCl as an epileptic seizure autoregulatory Gene therapeutic approach

Around 70 Million people worldwide are affected by epilepsy (estimates for Europe 0.6-0.7% of the general population) (http://www.who.int/mediacentre/factsheets/fs999/en/; accessed 10/05/2015), of whom at least 20% (14 million people) do not respond to commonly available drugs. Many antiepileptic drugs show a relatively narrow therapeutic window, and elicit a variety of serious side effects, mainly because they affect the whole brain. The only effective treatment option for focal-onset refractory epilepsy is surgical resection, where the region in which the epileptic seizures arise is removed. Although this invasive surgery can result in seizure freedom in 60 – 80% of patients, it is accompanied by a substantial risk of severe and irreversible side effects, including disturbance in motor function, vision, memory and language. This risk makes surgery inappropriate for the overwhelming majority of patients. New treatment options are therefore urgently required. Several mechanisms that make neuronal networks hyper-excitable have been identified in experimental and clinical epilepsy. Increased activity of excitable synapses, and subsequent increased synchronized glutamate (glu) release, is a common feature of these pathologies, and closely related to the definition of seizures as episodes of abnormal and excessive discharge of principal neurons. We developed a biochemical sensor which detects high levels of the excitatory neurotransmitter glu, which is increased in the cerebrospinal fluid (of patients) during seizures. In response to the increased glu concentration the sensor opens, and triggers an inhibitory Chloride current in affected neurons. This approach has the potential to decrease the disease-burden of a high number of epilepsy patients, for which currently no appropriate treatment options are available.

Data: CORDIS, © European Union