@article {Karaa10.1212 / WNL。0000000000207402,作者={阿梅尔Karaa和恩里科·贝尔蒂尼Valerio Carelli布鲁斯·H·科恩和格里高利·m·新奥集团Marni J福尔克和艾米Goldstein和Gr {\ '} inne Siobhan Gorman和理查德·哈斯和渡Hirano托马斯Klopstock所说和玫琳凯Koenig科妮莉亚Kornblum)和Lamperti和安娜雷曼和尼古拉Longo玛丽亚Judit Molnar和苏米特帕里克说汉族表象和罗伯特·D S Pitceathly罗素Saneto和费尔南多Scaglia Serenella Servidei马克线粒体和安东尼奥Toscano约翰L。K范霍夫和约翰活力和杰瑞Vockley和Jeffrey S Finman和大卫·布朗和詹姆斯Shiffer和Michelango曼库索和MMPOWER-3审判人员},title = {Elamipretide疗效和安全性的主要线粒体肌病患者:MMPOWER-3随机临床试验},elocation-id = {10.1212 / WNL。={2023}0000000000207402},年,doi = {10.1212 / WNL。出版商0000000000207402}= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={背景和目标:主要线粒体肌病(PMMs)包含一组遗传疾病,损害线粒体氧化磷酸化,首页不利影响身体功能、运动能力,和生活质量(QoL)。当前PMM护理解决症状,有限的临床影响,构成一个重要的治疗未满足的需求。我们从MMPOWER-3显示数据、关键阶段3,随机、双盲、安慰剂对照临床试验的有效性和安全性评估在参与者elamipretide genetically-confirmed PMM。方法:筛选后,合格的参与者被随机的1:1,24周接受elamipretide 40毫克/天或安慰剂皮下注射。主要疗效端点包括改变从基线到24周走在6分钟步行的距离测试(6 mwt),并在主节点上总疲劳线粒体肌病症状评估(PMMSA)。二次端点包括PMMSA最麻烦的症状评分、NeuroQoL疲劳短形式的分数,和病人{\ textendash}医生{\ textendash}的全球印象PMM症状。结果:参与者(N = 218)是随机的(N = 109 elamipretide;n = 109安慰剂)。平均年龄为45.6年(64 \ %的女性;94 \ %白色)。 The majority of participants (n=162 [74\%]) had mitochondrial DNA (mtDNA) mutations, with the remainder having nuclear DNA (nDNA) defects. At screening, the most frequent bothersome PMM symptom on the PMMSA was tiredness during activities (28.9\%). At baseline, mean distance walked on the 6MWT was 336.7{\textpm}81.2 meters, mean score for Total Fatigue on the PMMSA was 10.6{\textpm}2.5, and mean T-score for the Neuro-QoL Fatigue Short Form was 54.7{\textpm}7.5. The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA Total Fatigue Score (TFS). Between the participants receiving elamipretide versus placebo, the difference in the Least Squares Mean (SE) from baseline to Week 24 on distance walked on the 6MWT was -3.2 (95\% confidence interval,-18.7,12.3; p=0.69) meters and on the PMMSA Total Fatigue Score was -0.07 (95\% confidence interval,-0.10,0.26; p=0.37). Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity.Discussion: Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated.Trial Registration Information: Trial registered with clinicaltrials.gov, Clinical Trials Identifier: NCT03323749; submitted on October 12, 2017;first patient enrolled October 9, 2017. https://clinicaltrials.gov/ct2/show/NCT03323749?term=elamipretide\&draw=2\&rank=9Classification of Evidence: This study provides Class I evidence that elamipretide does not improve the 6 minute walk test or fatigue at 24 weeks compared to placebo in patients with primary mitochondrial myopathy.}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/early/2023/06/02/WNL.0000000000207402}, eprint = {//www.ez-admanager.com/content/early/2023/06/02/WNL.0000000000207402.full.pdf}, journal = {Neurology} }