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

作　　者：Katherine E.Olson Mai M.Abdelmoaty Krista L.Namminga Yaman Lu Helen Obaro Pamela Santamaria R.Lee Mosley Howard E.Gendelman 

机构地区：[1]Department of Pharmacology and Experimental Neuroscience,Center for Neurodegenerative Disorders,University of Nebraska Medical Center,Omaha,NE 68198,USA [2]Great Plains Center for Clinical and Translational Research,Nebraska Medicine,Omaha,NE,USA [3]Neurology Consultants of Nebraska,PC and Nebraska Medicine,Omaha,NE,USA

出　　处：《Translational Neurodegeneration》2023年第1期529-545,共17页转化神经变性病（英文）

基　　金：supported by National Institute of Neurological Disorders and Stroke Grant 5 R01NS034239-25 and private donations provided through the University of Nebraska Foundation.

摘　　要：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.

关 键 词：Parkinson’s disease Granulocyte-macrophage colony-stimulating factor Unified Parkinson’s Disease Rating Scale Regulatory T cells NEUROPROTECTION Sargramostim therapy 

分 类 号：R742.5[医药卫生—神经病学与精神病学]