Jay S Schneider1, Franca Cambi2, Stephen M Gollomp3, Hiroto Kuwabara4, James R Brašić4, Benjamin Leiby5, Stephanie Sendek6, Dean F Wong7. 1. Department of Pathology, Anatomy and Cell Biology and Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA 19107, United States. Electronic address: jay.schneider@jefferson.edu. 2. Dept. of Neurology, University of Pittsburgh School of Medicine and Pittsburgh VAMC, Pittsburgh, PA 15213, United States. 3. Division of Neurology, Lankenau Medical Center, Wynnewood, PA 19096, United States. 4. Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States. 5. Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States. 6. Department of Pathology, Anatomy and Cell Biology and Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA 19107, United States. 7. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Psychiatry and Behavior Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
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.
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.
Authors: Alan L Whone; Ray L Watts; A Jon Stoessl; Margaret Davis; Sven Reske; Claude Nahmias; Anthony E Lang; Olivier Rascol; Maria J Ribeiro; Philippe Remy; Werner H Poewe; Robert A Hauser; David J Brooks Journal: Ann Neurol Date: 2003-07 Impact factor: 10.422
Authors: Melanie Alpaugh; Danny Galleguillos; Juan Forero; Luis Carlos Morales; Sebastian W Lackey; Preeti Kar; Alba Di Pardo; Andrew Holt; Bradley J Kerr; Kathryn G Todd; Glen B Baker; Karim Fouad; Simonetta Sipione Journal: EMBO Mol Med Date: 2017-11 Impact factor: 12.137