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

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.

Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin(®)) injections in blepharospasm.

IncobotulinumtoxinA (Xeomin(®), NT 201) is a purified botulinum toxin type A free from accessory (complexing) proteins. Previous studies evaluated single sets of incobotulinumtoxinA injections for the treatment of blepharospasm. Individualized injection intervals and other potential determinants of efficacy and safety need to be evaluated in a prospective, longitudinal study. Subjects with blepharospasm who completed a ≤ 20 weeks double-blind, placebo-controlled main period entered a ≤ 69 weeks open-label extension period (OLEX) and received ≤ 5 additional incobotulinumtoxinA treatments at flexible doses (≤ 50 U per eye) and flexible injection intervals (minimum of 6 weeks). Outcome measures included Jankovic Rating Scale (JRS) (sumscore, severity subscore and frequency subscore), Blepharospasm Disability Index, and adverse events. All 102 subjects who completed the main period entered the OLEX; 82 subjects completed the study, 56 received the maximum five injections. From each injection visit to a control visit 6 weeks later, investigator-rated JRS sumscores and subscores, and patient-rated Blepharospasm Disability Index were significantly improved (p ≤ 0.001 for all). All scores were still significantly improved at trial termination compared with the first injection visit (p < 0.05 for all). The most frequently reported adverse events were eyelid ptosis (31.4 %) and dry eye symptoms (17.6 %). The injection interval had no impact on the incidence of adverse events (post hoc analysis). No subject developed neutralizing antibodies during the study. Repeated incobotulinumtoxinA injections, administered at flexible doses and injection intervals from 6 to 20 weeks according to subjects' needs, provide sustained efficacy in the treatment of blepharospasm with no new or unexpected safety risks.

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

The present single center, double-blind, delayed start study was conducted to examine possible symptomatic and disease-modifying effects of GM1 ganglioside in Parkinson's disease (PD). Seventy-seven subjects with PD were randomly assigned to receive GM1 for 120 weeks (early-start group) or placebo for 24 weeks followed by GM1 for 96 weeks (delayed-start group). Washout evaluations occurred at 1 and 2 years after the end of treatment. Seventeen additional subjects who received standard-of-care were followed for comparative information about disease progression. Primary outcome was change from baseline Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. At week 24, the early-start group had significant improvement in UPDRS motor scores vs. a significant worsening of scores in the delayed-start group. The early-start group also showed a sustained benefit vs. the delayed-start group at week 72 and at week 120. Both groups had significant symptom worsening during washout. This study provides evidence that GM1 use for 24 weeks was superior to placebo for improving motor symptoms and that extended GM1 use (up to 120 weeks) resulted in a lower than expected rate of symptom progression. The data from this small study suggest that GM1 may have symptomatic and potentially disease modifying effects on PD.

Repeatable battery for assessment of neuropsychological status in early Parkinson's disease.

Adequate reliability and valid factor structure are prerequisites for appropriate use of a measure in a population. Although the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) has been used to examine cognition in Parkinson's disease (PD), its reliability and factor structure have not been examined in this population. This study examined the reliability and factor structure of the RBANS in participants with de novo PD recruited for two NIH Exploratory Trials in Parkinson's Disease (NET-PD), using Cronbach's alpha and factor analysis. Confirmatory factor analysis (CFA) was implemented on the factor structure proposed in the RBANS manual, and exploratory factor analysis (EFA) was conducted to identify a valid factor structure given the proposed one was not supported. The RBANS exhibited poor reliability in participants with NET-PD. Cronbach's alpha ranged from 0.03 to 0.74 for the five domains and the full scale. CFA results indicated that the proposed factor structure in the RBANS manual was not supported in this sample. EFA identified a two-factor structure for six of the 12 RBANS items. Six items were eliminated due to low correlation with other items or severe ceiling effects. This new factor structure was validated by another CFA. The two domains have fair reliability. Cronbach's alpha ranged from 0.65 to 0.74 for the two factors in the two datasets. These results suggest that the current RBANS domain and total scores may not provide valid measurement of the neuropsychological status for patients with early PD.