Nightingale Helen, Pfeffer Gerald, Bargiela David, Horvath Rita, Chinnery Patrick F
Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK Department of Clinical Neurosciences, University of Calgary, Calgary, Canada Hotchkiss Brain Institute, at the University of Calgary, Calgary, Canada.
Brain. 2016 Jun;139(Pt 6):1633-48. doi: 10.1093/brain/aww081. Epub 2016 May 3.
Mitochondrial disorders are a diverse group of debilitating conditions resulting from nuclear and mitochondrial DNA mutations that affect multiple organs, often including the central and peripheral nervous system. Despite major advances in our understanding of the molecular mechanisms, effective treatments have not been forthcoming. For over five decades patients have been treated with different vitamins, co-factors and nutritional supplements, but with no proven benefit. There is therefore a clear need for a new approach. Several new strategies have been proposed acting at the molecular or cellular level. Whilst many show promise in vitro, the clinical potential of some is questionable. Here we critically appraise the most promising preclinical developments, placing the greatest emphasis on diseases caused by mitochondrial DNA mutations. With new animal and cellular models, longitudinal deep phenotyping in large patient cohorts, and growing interest from the pharmaceutical industry, the field is poised to make a breakthrough.
线粒体疾病是由核DNA和线粒体DNA突变导致的一组多样的使人衰弱的病症，这些突变会影响多个器官，通常包括中枢和外周神经系统。尽管我们对分子机制的理解取得了重大进展，但尚未出现有效的治疗方法。五十多年来，患者一直接受不同的维生素、辅助因子和营养补充剂治疗，但没有得到证实的益处。因此，显然需要一种新方法。已经提出了几种在分子或细胞水平上起作用的新策略。虽然许多策略在体外显示出前景，但有些策略的临床潜力值得怀疑。在这里，我们批判性地评估最有前景的临床前进展，尤其着重于由线粒体DNA突变引起的疾病。随着新的动物和细胞模型、对大量患者队列的纵向深度表型分析以及制药行业越来越浓厚的兴趣，该领域有望取得突破。
