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- W2149013651 abstract "Recombinant human glial cell line-derived neurotrophic factor (r-metHuGDNF) is a potent neuronal growth and survival factor that has been considered for clinical use in the treatment of Parkinson’s disease (PD). Here we present results of a 6-month toxicology study in rhesus monkeys conducted to support clinical evaluation of chronic intraputamenal infusion of r-metHuGDNF for PD. Monkeys (6–9/sex/group) were treated with 0 (vehicle), 15, 30, or 100 μg/day r-metHuGDNF by continuous unilateral intraputamenal infusion (150 μl/day flow rate) for 6 months; a subset of animals (2–3/sex/group) underwent a subsequent 3-month treatment-free recovery period. Notable observations included reduced food consumption and body weight at 100 μg/day and meningeal thickening underlying the medulla oblongata and/or overlying various spinal cord segments at 30 and 100 μg/day. In addition, multifocal cerebellar Purkinje cell loss (with associated atrophy of the molecular layer and, in some cases, granule cell loss) was observed in 4 monkeys in the 100-μg/day group. This cerebellar finding has not been observed in previous nonclinical studies evaluating r-metHuGDNF. The small number of affected animals precludes definitive conclusions regarding the pathogenesis of the cerebellar lesion, but the data support an association with r-metHuGDNF treatment." @default.
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- W2149013651 date "2007-12-01" @default.
- W2149013651 modified "2023-10-16" @default.
- W2149013651 title "Reprint: Six-Month Continuous Intraputamenal Infusion Toxicity Study of Recombinant Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (r-metHuGDNF) in Rhesus Monkeys" @default.
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- W2149013651 doi "https://doi.org/10.1177/01926230701481899" @default.
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