Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease

Trends Mol Med. 2021 Mar;27(3):263-279. doi: 10.1016/j.molmed.2020.09.013. Epub 2020 Oct 26.


Neurodegenerative diseases (NDDs) are a heterogeneous group of diseases that are characterized by the progressive loss of neurons leading to motor, sensory, and/or cognitive defects. Currently, NDDs are not curable and treatment focuses on alleviating symptoms and halting disease progression. Phenotypic heterogeneity between individual NDD patients, lack of robust biomarkers, the limited translational potential of experimental models, and other factors have hampered drug development for the treatment of NDDs. This review summarizes and discusses the use of induced pluripotent stem cell (iPSC) approaches for improving drug discovery and testing. It highlights challenges associated with iPSC modeling and also discusses innovative approaches such as brain organoids and microfluidic-based technology which will improve drug development for NDDs.

Keywords: brain organoids; drug development; iPSC; microfluidics; neurodegeneration; screening.

Publication types

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

MeSH terms

  • Brain / cytology
  • Brain / pathology
  • Cell Differentiation
  • Drug Development / methods*
  • Humans
  • Induced Pluripotent Stem Cells / transplantation*
  • Microfluidics / methods
  • Neurodegenerative Diseases / therapy*
  • Neurons / cytology
  • Neurons / pathology
  • Organoids / cytology
  • Organoids / pathology