期刊
TOXICOLOGIC PATHOLOGY
卷 35, 期 7, 页码 1013-1029出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/01926230701481899
关键词
GDNF; Parkinson's disease; toxicology; toxicity; cerebellum; Purkinje cell; monkey; infusion; putamen; rhesus
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 mu g/day r-metHuGDNF by continuous unilateral intraputamenal infusion (150 mu 1/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 mu g/day and meningeal thickening underlying the medulla oblongata and/or overlying various spinal cord segments at 30 and 100 mu g/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-mu g/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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据