Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy.
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.
Noè
Francesco
F
Department of Neuroscience, Mario Negri Inst for Pharmacol Res, Via G. la Masa 19, 20156 Milano, Italy.
Pool
Allan-Hermann
AH
Nissinen
Jari
J
Gobbi
Marco
M
Bland
Ross
R
Rizzi
Massimo
M
Balducci
Claudia
C
Ferraguti
Francesco
F
Sperk
Gunther
G
During
Matthew J
MJ
Pitkänen
Asla
A
Vezzani
Annamaria
A
D000818:Animals; D002908:Chronic Disease; D000229:Dependovirus / Q000235:genetics; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000628:therapy*; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D007267:Injections; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic / Q000379:methods; D014741:Video Recording
D009478:Neuropeptide Y