Genic therapy and epilepsy: antiepileptic action of intra-hippocampal injection of adeno-associated viral (AAV) gene of the neuropeptldes Y (AAV-NPY) in marmoset (Callithrix jacchus) submitted to pilocarpine model

• Grant number: 09/53647-6
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2010
• End date: April 30, 2012
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Miriam Marcela Blanco
• Grantee: Miriam Marcela Blanco
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 10/08189-7 - Genic therapy and epilepsy: antiepileptic action of intra-hippocampal injection of adenoassociated viral (AAV) gene of the neuropeptides y (AAV-NPY) in marmoset (Callithrix jacchus) submitted to pilocarpine model, BP.JP

Abstract

This research has a long-standing interest in understanding the basic mechanisms underlying epilepsy as well as in the development of improved therapeutic strategies. Here, we propose the development and characterization of a novel gene transfer approach. Specifically, the use of a defective (and harmless) viral vector to deliver the cDNA for an antiepileptic neuropeptide, neuropeptide Y (NPY), directly into the hippocampus, as a strategy to reduce or suppress seizures. Here, we propose to take this research a significant step forward, both in terms of looking more comprehensively at the physiological effects of the gene transfer, as well as using models which are more similar to the human condition. This proposal includes main parts: functional studies aimed at assessing the anticonvulsant effect of AAV-NPY vectors on spontaneous and recurrent seizures, and the possibility of preventing their occurrence; development and functional characterization of novel AA V serotypes and regulatable vectors suitable to switch off the transcription of the transgene when needed. Objective: we propose to investigate the hypothesis of that the NPY¬administration affects the development of the ictiogenesis and/or epiletogesesis process and thus to evaluate the development of a new antiepileptic strategy based in the transference of the intra-hippocampal injection of adeno-associated viral (AA V) gene of the neuropeptides Y (AA V - NPY) in marmoset in the pilocarpina model. Hypothesis: one expects that the superexpression generated for the vector of adenovirus-associate (AA V) of the gene of neuropeptídeo Y (NPY) can be to inhibit of the glutamatergic excitatory neurotransmission in hipocampal region, and possibility to generate the neuroprotection or to minimize the chronic events of the illness, being able to represent an efficient antiepileptic strategy. (AU)