Amel Karaa, Amy Goldstein, Bruce H Cohen, Richard H Haas, Jerry Vockley, Gráinne S Gorman, Michelangelo Mancuso
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引用次数: 0
摘要
原发性线粒体肌病(PMMs)是一组遗传性线粒体氧化磷酸化疾病,主要影响骨骼肌功能。目前还没有批准的PMM治疗方法,患者信息有限。国际RePOWER登记处(NCT03048617)评估了PMM的基因型和表型关系,并确定了MMPOWER-3 (elamipretide 3期研究)患者。RePOWER纳入了16-80岁的筛查和流动患者。有PMM的体征和/或症状(N = 376;60.4%的女性;平均[SD]年龄42.6[14.4]岁;~75%为mtDNA变异,~25%为nDNA变异)。收集基线信息、当前症状、生活质量和功能评估(6分钟步行测试[6MWT]、三次站起行走测试[3TUG]和5次坐立测试[5XSST])。大多数患者可获得认可的实验室和基因检测方法。大多数入组的PMM患者表现为进行性外眼肌麻痹和疲劳。观察到美国患者使用更多的医疗干预措施。与非美国患者相比,美国患者在6MWT(平均364.6 vs. 375.2 m)和5XSST(平均21.6 vs. 18.6 s)上表现不佳;美国患者在3TUG测试中表现更好(平均40.2秒vs 45.0秒)。RePOWER注册表提供了遗传证实的PMM患者的数据,从而提高了我们对PMM诊断和治疗的理解以及全球线粒体临床实践的差异。
RePOWER: An International, Prospective, Non-Interventional Registry of Patients With Primary Mitochondrial Myopathy.
Primary mitochondrial myopathies (PMMs), a group of genetic mitochondrial oxidative phosphorylation disorders, primarily affect skeletal muscle function. No approved treatments for PMM exist, and patient information is limited. The international RePOWER registry (NCT03048617) assessed genotypic and phenotypic relationships in PMM and identified patients for MMPOWER-3 (elamipretide Phase 3 study). RePOWER enrolled screened and ambulatory patients aged 16-80 years. With signs and/or symptoms of PMM (N = 376; 60.4% female; mean [SD] age 42.6 [14.4] years; ~75% with an mtDNA variant and ~25% with an nDNA variant). Baseline information, current symptoms, qualityoflife, and functional assessments (6-Minute Walk Test [6MWT], Triple-Timed Up-and-Go [3TUG] Test, and 5-Times Sit-to-Stand Test [5XSST]) were captured. Accredited laboratory and genetic testing methods were available to most patients. The majority of enrolled PMM patients presented with progressive external ophthalmoplegia and fatigue. US patients were observed to use more medical interventions. Compared to non-US patients, US patients did not perform as well on the 6MWT (mean 364.6 vs. 375.2 m) and 5XSST (mean 21.6 vs. 18.6 s); US patients performed better on the 3TUG test (mean 40.2 vs. 45.0 s). The RePOWER registry provided data on patients with genetically confirmed PMM, thereby improving our understanding of PMM diagnosis and treatment and the differences in global mitochondrial clinical practice.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease