GM1 GANGLIOSIDE EFFECTS ON PARKINSONS DISEASE

GM1 神经节苷脂对帕金森病的影响

• 批准号: 2842422
• 负责人: JAY S SCHNEIDER
• 金额: $ 51.76万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842422
• 关键词: Parkinson's disease; brain disorder chemotherapy; clinical research; clinical trials; corpus striatum; dopamine; gangliosides; human subject; human therapy evaluation; innervation; longitudinal human study; magnetic resonance imaging; neuropathology; neuroprotectants; pathologic process; single photon emission computed tomography

DESCRIPTION: (Verbatim from the Applicant's Abstract) In view of pre-clinical data indicating GM1 ganglioside effects on dopamine (DA) neuron survival, repair and terminal sprouting and preliminary clinical data indicating efficacy in treating Parkinson's Disease (PD), we propose to assess the extent to which GM1 treatment in PD patients stimulates DA terminal sprouting and/or slows the predicted loss of striatal DA terminals in these patients over time. This research has the following specific objectives: 1) Assess the relationship between clinical improvement and in vivo quantitation of the integrity of the DAergic innervation in patients with typical mild/moderate, levodopa-responsive PD in a randomized double blind placebo-controlled clinical trial of GM1 in PD. This work will verify, in a larger group of patients, previous positive effects of GM1 on PD and directly examine the extent to which significant symptomatic improvements with GM1 treatment are due to disease-modifying effects on rescue/repair of DA neurons and through sprouting of functional DAergic terminals in the striatum. 2) Assess the extent to which long-term use of GM1 ganglioside may modify or slow symptom progression in PD patients and study the relationship between the rate of symptom progression and the density of striatal DAergic terminals in GM1 and non-GM1-treated patients. This work will verify preliminary data showing slowed symptom progression with long-term (up to 2 years). GM1 use and examine the extent to which the stabilization or slowing of symptom progression in PD patients is accompanied by slowed loss of striatal DA terminals over time, compared to non-GM1-treated patietns. The first phase of the study is a single-center, double-blind, stratified, placebo-controlled, randomized parallel-group study with GM1 and placebo treatment groups. Primary efficacy measures will be change in Unified Parkinson's Disease Rating Scale (UPRDS) motor scores and TRODAT (i.e., the tropane derivative used to assess striatal dopamine reuptake site and terminal density) SPECT scans between baseline and 24 week follow-up. In the second phase of the study, patietns who were initially in the GM1 treatment group will be allowed to receive GM1 for 2 years in open extension. At the conclusion of the 2 year open extension study period, all patietns will receive a follow-up SPECT scan. A control group of patietns randomized at the outset of the study will also be seen at 6 month intervals over a 2 year period to assess symptom progression and will have SPECT scans performed at baseline and at 2 year follow-up for comparison. Results from this study will provide important new information on the natural progression of Parkinson's disease and could demonstrate for the first time, reparative terminal sprouting or a neuroprotective effect in this progressive neurodegenerative disorder.

描述：（逐字摘自申请人摘要）鉴于临床前 表明GM 1神经节苷脂对多巴胺（DA）神经元存活的影响的数据， 修复和终末发芽以及表明疗效的初步临床数据 在治疗帕金森病（PD）时，我们建议评估 PD患者中的GM 1治疗刺激DA末端发芽和/或减缓PD患者的DA末端发芽。 预测随着时间的推移，这些患者的纹状体DA终末丢失。这 研究有以下具体目标： 1)评估临床改善与体内试验之间的关系 定量分析DA能神经支配的完整性， 一项随机双盲研究中的典型轻度/中度、左旋多巴反应性PD GM 1在PD中的安慰剂对照临床试验。这项工作将验证，在一个 更大的患者组，既往GM 1对PD的积极作用和直接 检查GM 1显著症状改善的程度 治疗是由于对DA神经元的拯救/修复的疾病改善作用 以及通过纹状体中功能性DA能末梢的发芽。 2)评估长期使用GM 1神经节苷脂可能改变或 减缓PD患者的症状进展，并研究 症状进展率和纹状体DA能终末密度 GM 1和非GM 1治疗的患者。这项工作将核实初步数据 显示长期（长达2年）症状进展缓慢。GM 1使用和 检查症状进展的稳定或减缓程度 在PD患者中，伴随着纹状体DA终末的缓慢丢失， 时间，与非GM 1治疗的患者相比。 该研究的第一阶段是一项单中心、双盲、分层、 一项安慰剂对照、随机化、平行组的GM 1和安慰剂研究 治疗组。主要疗效指标将是统一的变更 帕金森病评定量表（UPRDS）运动评分和TRODAT（即，的 托烷衍生物用于评估纹状体多巴胺再摄取位点和终末 在基线和24周随访之间的SPECT扫描。在第二 在研究阶段，最初参加GM 1治疗组的患者将 允许接受GM 1开放延长2年。结束时 在2年开放扩展研究期内，所有患者将接受随访 SPECT扫描。在研究开始时随机分配的对照组患者 也将在2年内每隔6个月观察一次，以评估症状 并将在基线和2年时进行SPECT扫描 跟踪比较。 这项研究的结果将为自然界提供重要的新信息。 帕金森病的进展，并首次证明， 修复性终末发芽或神经保护作用， 神经退行性疾病