An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety,tolerability,and immune biomarkers from limited case numbers

Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been evaluated.Methods As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 months.Secondary goals included numbers of CD4+T cells and monocytes and motor functions.Hematologic,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/kg.After 2 years,drug use was discon-tinued for 3 months.This was then followed by an additional 6 months of treatment.Results Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone pain.On drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment.Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased.In the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin signaling.This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.Conclusions Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment.Confirmation in larger patient populations is planned in a future phase II evaluation.

The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study

Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations.

Tremor and clinical fluctuation are related to sleep disorders in Chinese patients with Parkinson’s disease

Objective:To study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease(PD).Methods:The Parkinson’s Disease Sleep Scale-Chinese Version(PDSS-CV)was used to evaluate the sleep disturbances of PD patients in a cross sectional study.The Unified Parkinson’s Disease Rating Scale(UPDRS)parts II-IV,and the Hoehn&Yahr(H&Y)stage were used to determine the level of motor function in PD and the severity of PD.The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD.The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS.This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University,in Guangzhou.Results:A total of 136 PD patients were included in this study.The overall total PDSS score in PD patients was 107.58±23.35 points(range:30–146).There were significant differences in the disease duration,the H&Y stage,and the UPDRS section subscores between groups of patients either with or without sleep disturbances(Kruskal-Wallis Test,p<0.05).There were significant negative correlations between PDSS scores and the UPDRS subscores,the H&Y stage and the disease duration(Spearman correlation,p<0.05).The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity,tremor intensity and clinical fluctuation(R2=0.22,F(3,132)=12.4,p<0.001).The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.Conclusions:The level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients’sleep disturbances.This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.