Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Mol Genet Metab. 2022 Sep-Oct;137(1-2):40-48. doi: 10.1016/j.ymgme.2022.07.003. Epub 2022 Jul 6.
Mitochondrial DNA (mtDNA) replication depends on the mitochondrial import of hundreds of nuclear encoded proteins that control the mitochondrial genome maintenance and integrity. Defects in these processes result in an expanding group of disorders called mtDNA maintenance defects that are characterized by mtDNA depletion and/or multiple mtDNA deletions with variable phenotypic manifestations. As it applies for mitochondrial disorders in general, current treatment options for mtDNA maintenance defects are limited. Lately, with the development of model organisms, improved understanding of the pathophysiology of these disorders, and a better knowledge of their natural history, the number of preclinical studies and existing and planned clinical trials has been increasing. In this review, we discuss recent preclinical studies and current and future clinical trials concerning potential therapeutic options for the different mtDNA maintenance defects.
线粒体 DNA（mtDNA）复制依赖于数百种核编码蛋白的线粒体导入，这些蛋白控制着线粒体基因组的维持和完整性。这些过程中的缺陷导致了一组不断扩大的疾病，称为 mtDNA 维持缺陷，其特征是 mtDNA 耗竭和/或多种 mtDNA 缺失，表现出不同的表型。由于这适用于一般的线粒体疾病，目前 mtDNA 维持缺陷的治疗选择有限。最近，随着模型生物的发展，对这些疾病病理生理学的认识不断提高，以及对其自然史的更好了解，越来越多的临床前研究和现有的和计划中的临床试验正在进行。在这篇综述中，我们讨论了最近的临床前研究以及目前和未来的临床试验，这些研究涉及不同 mtDNA 维持缺陷的潜在治疗选择。
