Concise Review: Induced Pluripotent Stem Cell-Based Drug Discovery for Mitochondrial Disease

Stem Cells. 2017 Jul;35(7):1655-1662. doi: 10.1002/stem.2637. Epub 2017 May 22.

Abstract

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.

Keywords: Drug discovery; Induced pluripotent stem cells; Mitochondria; Neurological disorders; Reprogramming; mtDNA.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • DNA, Mitochondrial / genetics
  • Drug Discovery / methods*
  • Gene Expression
  • High-Throughput Screening Assays
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / agonists
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Models, Biological
  • Mutation
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Organoids / drug effects
  • Organoids / metabolism
  • Organoids / pathology
  • Precision Medicine

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Neuroprotective Agents