Organoid and pluripotent stem cells in Parkinson's disease modeling: an expert view on their value to drug discovery

Expert Opin Drug Discov. 2020 Apr;15(4):427-441. doi: 10.1080/17460441.2020.1703671. Epub 2020 Jan 3.


Introduction: Parkinson's disease is a devastating neurodegenerative disorder preferentially involving loss of dopaminergic neurons in the substantia nigra, leading to typical motor symptoms. While there are still no therapeutics to modify disease course, recent work using induced pluripotent stem cell (iPSC) and 3D brain organoid models have provided further insight into Parkinson's disease pathogenesis and potential therapeutic targets.Areas covered: This review highlights the generation of iPSC neurons and neural organoids as models for studying Parkinson's disease. It further discusses the recent work using patient-derived neurons from both familial and sporadic forms of Parkinson's to study disease pathogenic phenotypes and pathways. It additionally provides an evaluation of iPSC neurons and organoid models for therapeutic development in Parkinson's.Expert opinion: The use of Parkinson's disease patient-derived neurons and organoids provides us with the exciting opportunity to directly investigate pathogenic mechanisms and test drug compounds in human neurons. Future studies will involve generating more sophisticated models of brain organoids, studying neuronal pathways using larger patient cohorts, and routinely assessing therapeutics in these models.

Keywords: GBA; Induced pluripotent stem cells; Parkinson’s disease; dopaminergic neurons; midbrain; neurodegeneration; organoid; therapeutics; α-synuclein.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antiparkinson Agents / pharmacology
  • Brain / metabolism
  • Brain / physiopathology
  • Dopaminergic Neurons / metabolism
  • Drug Discovery / methods*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Models, Biological*
  • Organoids / metabolism
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology


  • Antiparkinson Agents