Pumilio: a novel target to control epilepsy

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Current antiepileptic drugs are effective for approx. two-thirds of patients and are associated with significant side-effects. Better drugs are needed, but a lack of novel drug targets is a significant barrier. Our research using the fruit fly (Drosophila melanogaster) has identified a protein called Pumilio, which has favourable properties to treat epilepsy. Pumilio is part of what is termed a 'homeostatic mechanism'. These mechanisms are used by nerve cells to regulate their activity in order to maintain a level that is appropriate for normal behaviour. Increasing Pumilio levels is strongly anticonvulsant in Drosophila. We now wish to identify drugs that target Pumilio. We have undertaken a comprehensive drug screen and have identified avobenzone to increase Pumilio activity. As might be expected, avobenzone is strongly anticonvulsant in flies. This is an interdisciplinary research project that will initially synthesize analogues of avobenzone to produce active compounds with better drug characteristics (good solubility, low toxicity etc.). Compounds synthesised will be tested for anticonvulsant properties using Drosophila and zebrafish seizure models. Favourable compounds will be taken forward for testing in rodent generalized seizure models.