NPY/Y2 gene therapeutic overexpression in hippocampus of experimental Beagle dogs

people worldwide. Current treatment is only symptomatic and fails to control seizures in about 40% of patients. Gene therapy with NPY overexpression has emerged as an alternative treatment strategy for epilepsy, showing inhibitory effect on seizures in animal models. This effect seems to be mediated mostly via Y2 receptors, while Y1 receptor activation has an opposite outcome. To enhance NPY gene transfer effect on seizures, we additionally overexposed Y2 receipts using AAV vectors in the hippocampus of epileptic rats. We demonstrate that transgene Y2 receptors are functional and even potentiate transgene NPY effect on seizures. These data suggest that combinatorial NPY/Y2 gene therapy could be an alternative strategy to single NPY gene overexertion.