Neuropharmacological strategies for disease modification and prevention of the development of epilepsy

Current therapies for epilepsy are symptomatic, only suppressing the symptoms (seizures), but do not impact the development or progression of disease. Many groups around the world, including ours, are testing novel therapies to impact epileptogenesis, intervening very early in epilepsy development to limit the severity of disease, with some preclinical success. But most patients present at the clinic already experiencing seizures, so a more practical strategy would be to attempt to modify epilepsy disease progression. For this project, we will investigate whether our novel treatments can reverse epilepsy severity in chronic rat models of acquired and genetic epilepsy. We then evaluate if the animals are having less seizures, behavioural comorbidities and neuroimaging changes after the completion of treatment. If the results are positive, they would have major clinical implications in patients with already established acquired epilepsy. Moreover, the experimental drugs that we will be tested have a favourable safety profile in early phase clinical trials facilitating the translation of the results of this preclinical study into a clinical trial. Skills: The skills expected to be learnt from this project include: Small animal handling and neurosurgery (electrode implantations), animal models of temporal lobe epilepsy and genetic epilepsy, behavioural neuroscience, magnetic resonance imagining interpretation and analysis. Positron emission tomography interpretation and analysis.