Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy

F Noč, AH Pool, J Nissinen, M Gobbi, R Bland, M Rizzi… - Brain, 2008 - academic.oup.com
F Noč, AH Pool, J Nissinen, M Gobbi, R Bland, M Rizzi, C Balducci, F Ferraguti, G Sperk…
Brain, 2008academic.oup.com
Temporal lobe epilepsy remains amongst the most common and drug refractory of
neurological disorders. Gene therapy may provide a realistic therapeutic approach
alternative to surgery for intractable focal epilepsies. To test this hypothesis, we applied here
a gene therapy approach, using a recombinant adeno-associated viral (rAAV) vector
expressing the human neuropeptide Y (NPY) gene, to a progressive and spontaneous
seizure model of temporal lobe epilepsy induced by electrical stimulation of the temporal …
Abstract
Temporal lobe epilepsy remains amongst the most common and drug refractory of neurological disorders. Gene therapy may provide a realistic therapeutic approach alternative to surgery for intractable focal epilepsies. To test this hypothesis, we applied here a gene therapy approach, using a recombinant adeno-associated viral (rAAV) vector expressing the human neuropeptide Y (NPY) gene, to a progressive and spontaneous seizure model of temporal lobe epilepsy induced by electrical stimulation of the temporal pole of the hippocampus, which replicates many features of the human condition. rAAV-NPY or a control vector lacking the expression cassette (rAAV-Empty) was delivered into the epileptic rat hippocampi at an early progressive stage of the disease. Chronic epileptic rats were video-EEG monitored to establish pre-injection baseline recordings of spontaneous seizures and the effect of rAAV-NPY versus rAAV-Empty vector injection. Both non-injected stimulated controls and rAAV-empty injected rats showed a similar progressive increase of spontaneous seizure frequency consistent with epileptogenesis. The delivery of rAAV-NPY in epileptic rat brain leads to a remarkable decrease in the progression of seizures as compared to both control groups and this effect was correlated with the NPY over-expression in the hippocampus. Moreover, spontaneous seizure frequency was significantly reduced in 40% of treated animals as compared to their pre-injection baseline. Our data show that this gene therapy strategy decreases spontaneous seizures and suppresses their progression in chronic epileptic rats, thus representing a promising new therapeutic strategy.
Oxford University Press