GM1 GANGLIOSIDE EFFECTS ON PARKINSONS DISEASE

描述：(逐字摘自申请者摘要)鉴于临床前 数据显示GM1神经节苷脂对多巴胺(DA)神经元存活的影响， 修复和顶芽及显示疗效的初步临床数据 在治疗帕金森氏病(PD)时，我们建议评估 帕金森病患者GM1治疗刺激DA终末萌发和/或延缓 预测随着时间的推移，这些患者的纹状体DA终末的丢失。这 研究有以下具体目标： 1)评估临床改善与体内的关系 慢性阻塞性肺疾病患者多巴胺能神经支配完整性的定量研究 随机双盲试验中典型的轻/中度左旋多巴反应性帕金森病 GM1治疗帕金森病的安慰剂对照临床试验。这项工作将在一个 更大的患者组，以前GM1对PD的积极作用和直接 检查使用GM1后症状显著改善的程度 治疗是由于疾病改变对DA神经元的拯救/修复作用 并通过纹状体中功能性DAR能终末的萌发。 2)评估长期使用GM1神经节苷脂可能改变或 帕金森病患者的症状进展缓慢，并研究其与 精神分裂症患者症状进展率和纹状体DAR能终末密度 GM1和未接受GM1治疗的患者。这项工作将验证初步数据 长期(长达2年)表现出缓慢的症状进展。GM1使用和 检查症状进展的稳定或减缓程度 帕金森病患者伴有纹状体DA终末缓慢丢失 时间，与未接受GM1治疗的患者相比。 研究的第一阶段是单中心、双盲、分层、 使用GM1和安慰剂的安慰剂对照、随机平行组研究 治疗组。主要的疗效衡量标准将在统一 帕金森病评定量表(UPRDS)运动评分和TRODAT(即 托烷衍生物用于评估纹状体多巴胺再摄取的部位和终末 密度)SPECT扫描在基线和24周随访之间。在第二个 在研究阶段，最初属于GM1治疗组的患者将 允许在两年内接受GM1的开放延期。在……结束时 为期2年的开放式延长研究期，所有患者都将接受随访 SPECT扫描。一组在研究开始时随机选择的对照组患者 还将在两年内每隔6个月进行一次检查，以评估症状 进展，并将在基线和2年后进行SPECT扫描 随访以作对照。 这项研究的结果将为自然界提供重要的新信息 帕金森氏症的进展，并可能首次证明， 在这种进行性疾病中，修复性末端发芽或神经保护作用 神经退行性疾病。

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.