Max Delbrueck Center for Molecular Medicine (MDC), Mitochondrial and Cell Fate Reprogramming, Department of Neuroproteomics, Berlin, Germany.
Berlin Institute of Health (BIH), Berlin, Germany.
Stem Cells. 2017 Jul;35(7):1655-1662. doi: 10.1002/stem.2637. Epub 2017 May 22.
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease. iPSCs can be used to generate patient-specific neural cell models in which innovative compounds can be identified or validated. Here we discuss the promises and challenges of iPSC-based drug discovery for mitochondrial disease with a specific focus on neurological conditions. We anticipate that a proper use of the potent iPSC technology will provide critical support for the development of innovative therapies against these untreatable and detrimental disorders. Stem Cells 2017;35:1655-1662.
高淘汰率和资本损失困扰着药物发现过程。这在涉及神经表现且由核或线粒体 DNA 缺陷引起的线粒体疾病中尤为明显。由于个体患者之间症状的可变性以及缺乏可行的建模系统，这群异质疾病难以成为治疗靶点。诱导多能干细胞 (iPSC) 的使用可能会极大地改善针对线粒体疾病的有效疗法的寻找。iPSC 可用于生成患者特异性神经细胞模型，在此模型中可以鉴定或验证创新化合物。在这里，我们讨论了基于 iPSC 的药物发现治疗线粒体疾病的前景和挑战，特别关注神经系统疾病。我们预计，适当使用强大的 iPSC 技术将为针对这些无法治疗和有害疾病的创新疗法的开发提供关键支持。《干细胞》2017;35:1655-1662.
