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- W2162198479 abstract "Gene therapy approaches delivering neurotrophic factors have offered promising results in both preclinical and clinical trials of Parkinson's disease (PD). However, failure of glial cell line-derived neurotrophic factor in phase 2 clinical trials has sparked a search for other trophic factors that may retain efficacy in the clinic. Direct protein injections of one such factor, insulin-like growth factor (IGF)-1, in a rodent model of PD has demonstrated impressive protection of dopaminergic neurons against 6-hydroxydopamine (6-OHDA) toxicity. However, protein infusion is associated with surgical risks, pump failure, and significant costs. We therefore used lentiviral vectors to deliver Igf-1, with a particular focus on the novel integration-deficient lentiviral vectors (IDLVs). A neuron-specific promoter, from the human synapsin 1 gene, excellent for gene expression from IDLVs, was additionally used to enhance Igf-1 expression. An investigation of neurotrophic effects on primary rat neuronal cultures demonstrated that neurons transduced with IDLV-Igf-1 vectors had complete protection on withdrawal of exogenous trophic support. Striatal transduction of such vectors into 6-OHDA-lesioned rats, however, provided neither protection of dopaminergic substantia nigra neurons nor improvement of animal behavior." @default.
- W2162198479 created "2016-06-24" @default.
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- W2162198479 date "2015-11-01" @default.
- W2162198479 modified "2023-10-17" @default.
- W2162198479 title "Efficient Expression of <i>Igf-1</i> from Lentiviral Vectors Protects <i>In Vitro</i> but Does Not Mediate Behavioral Recovery of a Parkinsonian Lesion in Rats" @default.
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- W2162198479 doi "https://doi.org/10.1089/hum.2015.016" @default.
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