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

Abstract

Objective: GM1 ganglioside has been suggested as a treatment for Parkinson's disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally.

Methods: Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD [1]: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 years. Dynamic PET scans were performed over 90 min following injection of [(11)C]methylphenidate. Regional values of binding potential (BPND) were analyzed for several striatal volumes of interest.

Results: Clinical results for this subset of subjects were similar to those previously reported for the larger study group. ES subjects showed early symptomatic improvement and slow symptom progression over the study period. DS and Comparison subjects were initially on the same symptom progression trajectory but diverged once DS subjects received GM1 treatment. Imaging results showed significant slowing of BPND loss in several striatal regions in GM1-treated subjects and in some cases, an increased BPND in some striatal regions was detected after GM1 use.

Interpretation: Results of this pilot imaging study provide additional data to suggest a potential disease modifying effect of GM1 on PD. These results need to be confirmed in a larger number of subjects.

Keywords: Caudate; Dopamine transporter; GM1 ganglioside; PET; Parkinson's disease; Putamen.

Figure 1

Changes in Unified Parkinson’s Disease Rating Scale (UPDRS) Motor Subsection Scores for the subset of subjects participating in the imaging study. The mean (±SEM) change from baseline (observed scores) in Early-start (N = 15) and Delayed-start (N = 14) sub-study subjects and in the standard-of-care Comparison group (N = 11), assessed in the practically defined “off” condition. The dashed vertical line at week 24 indicates the end of study Phase I. The dashed vertical line at week 120 indicates the end of study Phase II. The horizontal dashed line indicates baseline level. An increase of score indicates symptom worsening; a decrease in score indicates symptom improvement.

Figure 2

Averaged striatal binding potential images at baseline (Week 0 for the Comparison group (C) subjects (N = 11)) [left panel] and at the transition point in the delayed start study (Week 24 for Delayed-start (DS: N = 14) [middle panel] and Early-start (ES: N = 15) [right panel] groups) (top row) and averaged images obtained 2 years later at the end of the second phase of study during which all treatment subjects used GM1 ganglioside. Images show less loss of BP_ND over time in ES subjects and DS subjects versus Comparison group subjects. The far right panel demonstrates the averaged images of the MRIs of all participants.