‘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

doi:10.1016/j.tips.2022.03.001

‘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 journal › Review article › peer-review

2 Scopus citations

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	https://doi.org/10.1016/j.tips.2022.03.001
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tips.2022.03.001

Cite this

@article{3734bb4e145a4996b9e5bd7a9bb77690,

title = "{\textquoteleft}Channeling{\textquoteright} therapeutic discovery for epileptic encephalopathy through iPSC technologies",

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.",

keywords = "KCNQ2, SCN1A, SCN2A, developmental and epileptic encephalopathies (DEEs), induced pluripotent stem cells (iPSCs), ion channel genes",

author = "Dina Simkin and Christina Ambrosi and Marshall, {Kelly A.} and Williams, {Luis A.} and Jordyn Eisenberg and Mennat Gharib and Dempsey, {Graham T.} and George, {Alfred L.} and McManus, {Owen B.} and Evangelos Kiskinis",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = may,

doi = "10.1016/j.tips.2022.03.001",

language = "English (US)",

volume = "43",

pages = "392--405",

journal = "Trends in Pharmacological Sciences",

issn = "0165-6147",

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TY - JOUR

T1 - ‘Channeling’ therapeutic discovery for epileptic encephalopathy through iPSC technologies

AU - Simkin, Dina

AU - Ambrosi, Christina

AU - Marshall, Kelly A.

AU - Williams, Luis A.

AU - Eisenberg, Jordyn

AU - Gharib, Mennat

AU - Dempsey, Graham T.

AU - George, Alfred L.

AU - McManus, Owen B.

AU - Kiskinis, Evangelos

N1 - Funding Information: 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. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

KW - KCNQ2

KW - SCN1A

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KW - developmental and epileptic encephalopathies (DEEs)

KW - induced pluripotent stem cells (iPSCs)

KW - ion channel genes

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‘Channeling’ therapeutic discovery for epileptic encephalopathy through iPSC technologies

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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