GM1 Ganglioside Effects on Parkinson's Disease

描述（由申请人提供）：帕金森病（PD）是一种缓慢但持续进展的神经退行性疾病，导致临床症状的时间依赖性恶化。目前还没有确定的药物可以明确地减缓或阻止PD的进展，或实质上预防PD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、增强受损神经元的修复、修复现有神经病理缺陷、恢复或增强多巴胺（DA）系统残余部分的功能和/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一种治疗方法。体外和体内研究表明，GM1可拯救受损的DA神经元，刺激DAergic神经元的存活和修复以及功能性DAergic末梢的萌发，增加纹状体中DA水平，上调残余神经元的DA合成能力。PD患者GM1的初步临床研究表明，短期使用GM1的患者临床改善，使用GM1 2至5年的患者症状进展最小，停止长期使用GM1后症状恢复进展。

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.