GM1 GANGLIOSIDE EFFECTS ON PARKINSONS DISEASE

描述：（摘自申请人摘要）鉴于临床前

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.