‘Channeling’ therapeutic discovery for epileptic encephalopathy through iPSC technologies

Dina Simkin, Christina Ambrosi, Kelly A. Marshall, Luis A. Williams, Jordyn Eisenberg, Mennat Gharib, Graham T. Dempsey, Alfred L. George, Owen B. McManus*, Evangelos Kiskinis

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-405
Number of pages14
JournalTrends in Pharmacological Sciences
Volume43
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • KCNQ2
  • SCN1A
  • SCN2A
  • developmental and epileptic encephalopathies (DEEs)
  • induced pluripotent stem cells (iPSCs)
  • ion channel genes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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