Mitochondrial disease in adults: what's old and what's new?
Mitochondrial disease in adults: what's old and what's new?
复制标题
成人的线粒体疾病：什么是旧的，什么是新的？
DOI：
10.15252/emmm.201505079
复制
发表时间：
2015-12
影响因子：
11.1
通讯作者：
Chinnery PF
中科院分区：
文献类型：
--
作者：
Chinnery PF
十年前，有一种新兴的观点认为，成人线粒体疾病的分子基础很大程度上是已知的，临床表型已经得到了很好的描述。没有什么比这更离谱的了。大量患者队列的建立揭示了临床表现的新方面，这是以前没有意识到的。随着时间的推移，这种方法开始提供对成年人线粒体疾病自然历史的准确理解。在下一代测序技术的支持下，分子诊断学的进步已经确定了新的分子机制。最近描述的线粒体疾病表型有不同的原因，但有共同的机制主题。特别是，线粒体DNA维持障碍已成为成人线粒体疾病的主要原因。进行性mtDNA耗竭和mtDNA突变的积累解释了一些临床特征，但导致mtDNA异常的遗传和细胞过程在每一种情况下都不完全清楚。不幸的是，除了几个具体的例子外，成人线粒体疾病的治疗还没有到来。然而，国际财团的建立和首个跨国随机对照试验，在制药业兴趣日益浓厚的支撑下，为近期取得重大进展铺平了道路。因此，成人线粒体医学还处于初级阶段，挑战是利用对其分子和细胞基础的新理解来开发对患者真正有益的治疗方法。
Ten years ago, there was an emerging view that the molecular basis for adult mitochondrial disorders was largely known and that the clinical phenotypes had been well described. Nothing could have been further from the truth. The establishment of large cohorts of patients has revealed new aspects of the clinical presentation that were not previously appreciated. Over time, this approach is starting to provide an accurate understanding of the natural history of mitochondrial disease in adults. Advances in molecular diagnostics, underpinned by next generation sequencing technology, have identified novel molecular mechanisms. Recently described mitochondrial disease phenotypes have disparate causes, and yet share common mechanistic themes. In particular, disorders of mtDNA maintenance have emerged as a major cause of mitochondrial disease in adults. Progressive mtDNA depletion and the accumulation of mtDNA mutations explain some of the clinical features, but the genetic and cellular processes responsible for the mtDNA abnormalities are not entirely clear in each instance. Unfortunately, apart from a few specific examples, treatments for adult mitochondrial disease have not been forthcoming. However, the establishment of international consortia, and the first multinational randomised controlled trial, have paved the way for major progress in the near future, underpinned by growing interest from the pharmaceutical industry. Adult mitochondrial medicine is, therefore, in its infancy, and the challenge is to harness the new understanding of its molecular and cellular basis to develop treatments of real benefit to patients.