title: Neuropeptide Y overexpression using recombinant adeno-associated viral vectors.
abstract: Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of "therapeutic" genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.
authors.affiliation: Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano 20156, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Noé
authors.forename: Angelisa
authors.initials: A
authors.lastname: Frasca
authors.forename: Claudia
authors.initials: C
authors.lastname: Balducci
authors.forename: Mirjana
authors.initials: M
authors.lastname: Carli
authors.forename: Gunther
authors.initials: G
authors.lastname: Sperk
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraguti
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkänen
authors.forename: Ross
authors.initials: R
authors.lastname: Bland
authors.forename: Helen
authors.initials: H
authors.lastname: Fitzsimons
authors.forename: Matthew
authors.initials: M
authors.lastname: During
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani