'Channeling' therapeutic discovery for epileptic encephalopathy through iPSC technologies

Trends Pharmacol Sci. 2022 May;43(5):392-405. doi: 10.1016/j.tips.2022.03.001.


Induced pluripotent stem cell (iPSC) and gene editing technologies have revolutionized the field of in vitro disease modeling, granting us access to disease-pertinent human cells of the central nervous system. These technologies are particularly well suited for the study of diseases with strong monogenic etiologies. Epilepsy is one of the most common neurological disorders in children, with approximately half of all genetic cases caused by mutations in ion channel genes. These channelopathy-associated epilepsies are clinically diverse, mechanistically complex, and hard to treat. Here, we review the genetic links to epilepsy, the opportunities and challenges of iPSC-based approaches for developing in vitro models of channelopathy-associated disorders, the available tools for effective phenotyping of iPSC-derived neurons, and discuss the potential therapeutic approaches for these devastating diseases.

Keywords: KCNQ2; SCN1A; SCN2A; developmental and epileptic encephalopathies (DEEs); induced pluripotent stem cells (iPSCs); ion channel genes.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Channelopathies*
  • Child
  • Epilepsy* / genetics
  • Epilepsy* / therapy
  • Humans
  • Induced Pluripotent Stem Cells*
  • Mutation
  • Neurons