Abstract
Huntington's disease (HD) is a devastating neurodegenerative disease characterized by the selective loss of neurons in the striatum and cerebral cortex. This study tested the hypothesis that an adenoassociated viral (AAV2) vector encoding for the trophic factor neurturin (NTN) could provide neuroprotection in the rat 3-nitropropionic acid (3NP) model of HD. Rats received AAV2-NTN (CERE-120), AAV2-eGFP or Vehicle, followed 4 weeks later by the mitochondrial toxin 3NP. 3NP induced motor impairments were observed on the rotarod test, the platform test, and a clinical rating scale in all groups. However, each of these deficits was attenuated by AAV2-NTN (CERE-120). Stereological counts revealed a significant protection of NeuN-ir striatal neurons from 3NP toxicity by AAV2-NTN. These data support the concept that AAV2-NTN might be a valuable treatment for patients with Huntington's disease.
MeSH terms
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Animals
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Cell Count
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Cell Death / genetics
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism*
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Corpus Striatum / physiopathology
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Cytoprotection / genetics
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DNA-Binding Proteins
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Dependovirus / genetics
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Disease Models, Animal
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Gene Transfer Techniques / trends
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Genetic Therapy / methods*
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Genetic Vectors / genetics
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Huntington Disease / chemically induced
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Huntington Disease / genetics
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Huntington Disease / therapy*
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Male
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Motor Activity / genetics
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Nerve Degeneration / physiopathology
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Nerve Degeneration / prevention & control
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Nerve Degeneration / therapy*
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / pathology
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Neurotoxins
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Neurturin / genetics*
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Neurturin / therapeutic use
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Nitro Compounds
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Nuclear Proteins / metabolism
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Propionates
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Rats
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Rats, Inbred Lew
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Recovery of Function / genetics
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Treatment Outcome
Substances
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DNA-Binding Proteins
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Nerve Tissue Proteins
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NeuN protein, mouse
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Neurotoxins
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Neurturin
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Nitro Compounds
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Nrtn protein, rat
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Nuclear Proteins
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Propionates
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3-nitropropionic acid