GM1 Ganglioside Effects on Parkinson's Disease

GM1 神经节苷脂对帕金森病的作用

• 批准号: 7237294
• 负责人: JAY S SCHNEIDER
• 金额: $ 59.97万
• 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 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7237294
• 关键词: Affect; Clinical; Clinical Research; Code; Contracts; Controlled Clinical Trials; Corpus striatum structure; Disease; Disease Progression; Dopamine; Double-Blind Method; Enrollment; Facility Construction Funding Category; Funding; Future; Ganglioside GM1; Gangliosides; Goals; Image; In Vitro; Italy; Label; Levodopa; Manufacturer Name; Measures; Neurodegenerative Disorders; Neurons; Neuroprotective Agents; Numbers; Parkinson Disease; Parkinsonian Disorders; Patients; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Population; Positron-Emission Tomography; Randomized; Recruitment Activity; Request for Applications; Research; Residual state; Role; Signs and Symptoms; Site; Symptoms; Time; Work; clinical efficacy; dopamine system; dopamine transporter; dopaminergic neuron; drug testing; functional decline; functional disability; improved; in vivo; nerve supply; panacea; programs; repaired; research clinical testing

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is a slowly but relentlessly progressive neurodegenerative disorder resulting in a time-dependent worsening of clinical symptoms. No drug has yet been identified that definitively slows or stops the progression of PD or substantially forestalls the inevitable functional decline in PD patients. Thus, disease modifying drugs that can modify clinical progression, enhance repair of damaged neurons, remediate existing neuropathological deficits, restore or enhance function of residual parts of the dopamine (DA) system and/or activate compensatory mechanisms are sorely needed. GM1 ganglioside may be such a treatment. In vitro and in vivo studies have shown GM1 to rescue damaged DA neurons, stimulate survival and repair of DAergic neuron and sprouting of functional DAergic terminals, increase DA levels in the striatum and upregulate DA synthetic capacity of residual neurons. Preliminary clinical studies of GM1 in PD patients have shown clinical improvements in patients with short-term use of GM1 and minimal symptom progression in patients with 2 to 5 years of GM1 use with resumed progression of symptoms following discontinuation of long-term GM1 use. The specific aims of this research are: 1) Assess the clinical efficacy of GM1 and the relationship between clinical improvement and in vivo quantitation of the integrity of the striatal DAergic innervation (assessed by PET imaging of the dopamine transporter site) in patients with typical mild/moderate PD in a randomized double blind placebo-controlled clinical trial. Working hypothesis: GM1 ganglioside treatment will result in symptomatic improvements related to effects on damaged but viable DA neurons and this may be accomplished through sprouting of functional DAergic terminals in the striatum. 2) Assess the extent to which long-term (2 years) use of GM1 ganglioside may stabilize symptoms or slow symptom/disease progression in PD patients (using clinical evaluations and PET imaging of the dopamine transporter as a surrogate measure). Working hypothesis: Long-term GM1 use will stabilize symptoms or slow the progression of symptoms in PD patients and this may be accompanied by reduced loss of striatal DA terminals over time.

描述（由申请人提供）：帕金森病（PD）是一种缓慢但持续进行的神经退行性疾病，导致临床症状随时间恶化。目前尚未发现任何药物能够明确减缓或阻止帕金森病的进展，或显着预防帕金森病患者不可避免的功能衰退。因此，迫切需要能够改变临床进展、增强受损神经元修复、修复现有神经病理缺陷、恢复或增强多巴胺（DA）系统剩余部分的功能和/或激活代偿机制的疾病修饰药物。 GM1神经节苷脂可能就是这样的治疗方法。体外和体内研究表明，GM1可以拯救受损的DA神经元，刺激DAergic神经元的存活和修复以及功能性DAergic末梢的萌芽，增加纹状体中的DA水平并上调残余神经元的DA合成能力。 GM1 在 PD 患者中的初步临床研究表明，短期使用 GM1 的患者临床改善，使用 2 至 5 年 GM1 的患者症状进展最小，但长期停止使用 GM1 后症状恢复进展。 本研究的具体目标是： 1) 在一项随机双盲安慰剂对照临床试验中，评估 GM1 对典型轻度/中度 PD 患者的临床疗效以及临床改善与纹状体 DAergic 神经支配完整性的体内定量（通过多巴胺转运蛋白位点 PET 成像评估）之间的关系。工作假设：GM1 神经节苷脂治疗将导致与受损但存活的 DA 神经元的影响相关的症状改善，这可能通过纹状体中功能性 DAergic 终端的萌芽来实现。 2) 评估长期（2 年）使用 GM1 神经节苷脂可以在多大程度上稳定 PD 患者的症状或减缓症状/疾病进展（使用多巴胺转运蛋白的临床评估和 PET 成像作为替代措施）。工作假设：长期使用 GM1 将稳定 PD 患者的症状或减缓症状的进展，并且随着时间的推移，这可能伴随着纹状体 DA 末端损失的减少。

项目成果

GM1 ganglioside in Parkinson's disease: Pilot study of effects on dopamine transporter binding.

• DOI: 10.1016/j.jns.2015.06.028
• 发表时间: 2015-09-15
• 期刊: Journal of the neurological sciences
• 影响因子: 4.4
• 作者: Schneider JS;Cambi F;Gollomp SM;Kuwabara H;Brašić JR;Leiby B;Sendek S;Wong DF
• 通讯作者: Wong DF

Behavioral persistence deficit in Parkinson's disease patients.

帕金森病患者的行为持续性缺陷。

• DOI: 10.1111/j.1468-1331.2006.01647.x
• 发表时间: 2007
• 期刊: European journal of neurology
• 影响因子: 5.1
• 作者: Schneider,JS

A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients.

• DOI: 10.1016/j.jns.2012.10.024
• 发表时间: 2013-01-15
• 期刊: JOURNAL OF THE NEUROLOGICAL SCIENCES
• 影响因子: 4.4
• 作者: Schneider, Jay S.;Gollomp, Stephen M.;Sendek, Stephanie;Colcher, Amy;Cambi, Franca;Du, Wei
• 通讯作者: Du, Wei

Relationship between Motor Symptoms, Cognition, and Demographic Characteristics in Treated Mild/Moderate Parkinson's Disease.

• DOI: 10.1371/journal.pone.0123231
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Schneider JS;Sendek S;Yang C
• 通讯作者: Yang C