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 language | English (US) |
---|---|
Pages (from-to) | 392-405 |
Number of pages | 14 |
Journal | Trends in Pharmacological Sciences |
Volume | 43 |
Issue number | 5 |
DOIs | |
State | Published - May 2022 |
Funding
This work was supported by the US National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) U54NS10887 and R21NS125503 and the New York Stem Cell Foundation . E.K. is a Les Turner ALS Center Investigator and a New York Stem Cell Foundation–Robertson Investigator.
Keywords
- KCNQ2
- SCN1A
- SCN2A
- developmental and epileptic encephalopathies (DEEs)
- induced pluripotent stem cells (iPSCs)
- ion channel genes
ASJC Scopus subject areas
- Toxicology
- Pharmacology