Advancing drug discovery for neurological disorders using ipsc-derived neural organoids

Gianluca Costamagna, Giacomo Pietro Comi, Stefania Corti

Research output: Contribution to journalReview articlepeer-review


In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural or-ganoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adop-tion of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valua-ble tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its transla-tion toward large-scale drug screening for neurological disorders.

Original languageEnglish
Article number2659
Number of pages21
JournalInternational Journal of Molecular Sciences
Issue number5
Publication statusPublished - Mar 1 2021


  • Bioengineering
  • Brain organoids
  • CRISPR-Cas9
  • Disease modeling
  • Drug discovery
  • Induced pluripotent stem cells (iPSCs)
  • Machine learning
  • Neurological diseases
  • Organoid imaging
  • Single-cell sequencing

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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