Steele Hannah E, Horvath Rita, Lyon Jon J, Chinnery Patrick F
Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
GlaxoSmithKline, Molecular Safety and Disposition, Ware, SG12 0DP, UK.
Brain. 2017 Oct 1;140(10):2530-2540. doi: 10.1093/brain/awx168.
Mitochondrial disorders are genetically determined metabolic diseases due to a biochemical deficiency of the respiratory chain. Given that multi-system involvement and disease progression are common features of mitochondrial disorders they carry substantial morbidity and mortality. Despite this, no disease-modifying treatments exist with clear clinical benefits, and the current best management of mitochondrial disease is supportive. Several therapeutic strategies for mitochondrial disorders are now at a mature preclinical stage. Some are making the transition into early-phase patient trials, but the lack of validated biomarkers of disease progression presents a challenge when developing new therapies for patients. This update discusses current biomarkers of mitochondrial disease progression including metabolomics, circulating serum markers, exercise physiology, and both structural and functional imaging. We discuss the advantages and disadvantages of each approach, and consider emerging techniques with a potential role in trials of new therapies.
线粒体疾病是由于呼吸链生化缺陷导致的遗传性代谢疾病。鉴于多系统受累和疾病进展是线粒体疾病的常见特征，它们具有很高的发病率和死亡率。尽管如此，目前尚无具有明确临床益处的疾病修饰治疗方法，线粒体疾病目前的最佳管理方式是支持性治疗。目前有几种针对线粒体疾病的治疗策略已处于成熟的临床前阶段。一些正在向早期患者试验过渡，但在为患者开发新疗法时，缺乏经过验证的疾病进展生物标志物是一个挑战。本综述讨论了线粒体疾病进展的当前生物标志物，包括代谢组学、循环血清标志物、运动生理学以及结构和功能成像。我们讨论了每种方法的优缺点，并考虑了在新疗法试验中可能发挥作用的新兴技术。
