Pluripotent Stem Cell-Based Drug Screening Reveals Cardiac Glycosides as Modulators of Myotonic Dystrophy Type 1

There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in al...

Full description

Saved in:
Bibliographic Details
Published iniScience Vol. 11; pp. 258 - 271
Main Authors Maury, Yves, Poydenot, Pauline, Brinon, Benjamin, Lesueur, Lea, Gide, Jacqueline, Roquevière, Sylvain, Côme, Julien, Polvèche, Hélène, Auboeuf, Didier, Alexandre Denis, Jérome, Pietu, Geneviève, Furling, Denis, Lechuga, Marc, Baghdoyan, Sandrine, Peschanski, Marc, Martinat, Cécile
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 25.01.2019
Elsevier
Subjects
Cell Biology
Life Sciences
Molecular Biology
Pharmaceutical sciences
Pharmacology
Physiology
Molecular Biology
Physiology
Cell Biology
Online AccessGet full text
ISSN2589-0042
2589-0042
DOI10.1016/j.isci.2018.12.019

Cover

Abstract There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases. [Display omitted] •Myotonic dystrophy type 1 hPSCs were adapted for high content screening•FDA-approved cardiac glycosides normalize in vitro and in vivo DM1 biological markers•Cardiac glycosides synergize with the ERK pathway to normalize DM1 biomarkers•This study emphasizes the value of human pluripotent stem cells for drug discovery Physiology; Molecular Biology; Cell Biology
AbstractList There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases. : Physiology; Molecular Biology; Cell Biology Subject Areas: Physiology, Molecular Biology, Cell Biology
There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases.
There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases. [Display omitted] •Myotonic dystrophy type 1 hPSCs were adapted for high content screening•FDA-approved cardiac glycosides normalize in vitro and in vivo DM1 biological markers•Cardiac glycosides synergize with the ERK pathway to normalize DM1 biomarkers•This study emphasizes the value of human pluripotent stem cells for drug discovery Physiology; Molecular Biology; Cell Biology
There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases.There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases.
There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors, resulting in alternative splicing misregulation. By combining human mutated pluripotent stem cells and phenotypic drug screening, we revealed that cardiac glycosides act as modulators for both upstream nuclear aggregations of DMPK mRNAs and several downstream alternative mRNA splicing defects. However, these occurred at different drug concentration ranges. Similar biological effects were recorded in a DM1 mouse model. At the mechanistic level, we demonstrated that this effect was calcium dependent and was synergic with inhibition of the ERK pathway. These results further underscore the value of stem-cell-based assays for drug discovery in monogenic diseases. • Myotonic dystrophy type 1 hPSCs were adapted for high content screening • FDA-approved cardiac glycosides normalize in vitro and in vivo DM1 biological markers • Cardiac glycosides synergize with the ERK pathway to normalize DM1 biomarkers • This study emphasizes the value of human pluripotent stem cells for drug discovery Physiology; Molecular Biology; Cell Biology
Author Peschanski, Marc
Poydenot, Pauline
Pietu, Geneviève
Baghdoyan, Sandrine
Martinat, Cécile
Alexandre Denis, Jérome
Gide, Jacqueline
Côme, Julien
Auboeuf, Didier
Brinon, Benjamin
Furling, Denis
Lechuga, Marc
Maury, Yves
Polvèche, Hélène
Lesueur, Lea
Roquevière, Sylvain
AuthorAffiliation 2 INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
1 CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
3 LBMC, 69007 Lyon, France
4 Sorbonne Universités UPMC Univ Paris 06, INSERM, Centre de Recherche en Myologie - UMRS974, Institut de Myologie, 75013 Paris, France
AuthorAffiliation_xml – name: 3 LBMC, 69007 Lyon, France
– name: 1 CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– name: 2 INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
– name: 4 Sorbonne Universités UPMC Univ Paris 06, INSERM, Centre de Recherche en Myologie - UMRS974, Institut de Myologie, 75013 Paris, France
Author_xml – sequence: 1
  givenname: Yves
  surname: Maury
  fullname: Maury, Yves
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 2
  givenname: Pauline
  surname: Poydenot
  fullname: Poydenot, Pauline
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 3
  givenname: Benjamin
  surname: Brinon
  fullname: Brinon, Benjamin
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 4
  givenname: Lea
  surname: Lesueur
  fullname: Lesueur, Lea
  organization: INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 5
  givenname: Jacqueline
  surname: Gide
  fullname: Gide, Jacqueline
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 6
  givenname: Sylvain
  surname: Roquevière
  fullname: Roquevière, Sylvain
  organization: INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 7
  givenname: Julien
  surname: Côme
  fullname: Côme, Julien
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 8
  givenname: Hélène
  surname: Polvèche
  fullname: Polvèche, Hélène
  organization: LBMC, 69007 Lyon, France
– sequence: 9
  givenname: Didier
  surname: Auboeuf
  fullname: Auboeuf, Didier
  organization: LBMC, 69007 Lyon, France
– sequence: 10
  givenname: Jérome
  surname: Alexandre Denis
  fullname: Alexandre Denis, Jérome
  organization: INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 11
  givenname: Geneviève
  surname: Pietu
  fullname: Pietu, Geneviève
  organization: INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 12
  givenname: Denis
  surname: Furling
  fullname: Furling, Denis
  organization: Sorbonne Universités UPMC Univ Paris 06, INSERM, Centre de Recherche en Myologie - UMRS974, Institut de Myologie, 75013 Paris, France
– sequence: 13
  givenname: Marc
  surname: Lechuga
  fullname: Lechuga, Marc
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 14
  givenname: Sandrine
  surname: Baghdoyan
  fullname: Baghdoyan, Sandrine
  organization: INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 15
  givenname: Marc
  surname: Peschanski
  fullname: Peschanski, Marc
  organization: CECS, I-STEM, AFM, 91100 Corbeil-Essonnes, France
– sequence: 16
  givenname: Cécile
  surname: Martinat
  fullname: Martinat, Cécile
  email: cmartinat@istem.fr
  organization: INSERM, UMR 861, UEVE, ISTEM, AFM, 91100 Corbeil-Essonnes, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30639849$$D View this record in MEDLINE/PubMed
https://hal.sorbonne-universite.fr/hal-01984689$$DView record in HAL
BookMark eNp9Uk1rGzEUXEpKk7r5Az0UHduDXX3tWoJSSJ02CTi0NOlZaKW3tsx6tZG0Bv_7auukJDkEBBJPM_OGN-9tcdT5DoriPcEzgkn1eTNz0bgZxUTMCJ1hIl8VJ7QUcooxp0eP3sfFaYwbjDHNh8vqTXHMcMWk4PKk6H-1Q3C9T9AldJNgixbQttNvOoJF52FYoRsTADrXrdBv2IFuI1roYJ026KLdGx-dhYh0RNfeDq1OPkTkG3S998l3zqDzfUzB9-s9ut33gMi74nWTReD0_p4Uf358v11cTpc_L64WZ8upKcsyTY3BNWG6ZFLS0mJGhOGNZmwuKg0EuKW6LitiOK4FMdJWQgMteSkyQTc1Y5Pi6qBrvd6oPritDnvltVP_Cj6slA7JmRYUISAZb0hZC8bnlulGSJxbcmqYNrbKWl8PWv1Qb8GaPKug2yeiT386t1Yrv1MVo3ORPU2KTweB9TPa5dlSjbUcn-CVkDuSsR_vmwV_N0BMapuTzqHoDvwQFSVzyZis-Ojrw2Nf_5Uf4s0AcQCY4GMM0Cjjkk7OjzZdqwhW4zKpjRqXSY3LpAgd3WQqfUZ9UH-R9OVAgpzszkFQGQGdAesCmJRH716i_wWjJ-Ji
CitedBy_id crossref_primary_10_1038_s41598_022_26614_z
crossref_primary_10_1055_a_2348_2803
crossref_primary_10_1111_nan_12876
crossref_primary_10_3390_cells12040571
crossref_primary_10_1093_hmg_ddab218
crossref_primary_10_3389_fphar_2022_856804
crossref_primary_10_1016_j_nmd_2020_03_011
Cites_doi 10.1096/fj.201700700R
10.1158/0008-5472.CAN-10-1037
10.1038/mtna.2015.35
10.1016/j.gde.2017.03.007
10.1038/srep42522
10.1093/hmg/ddt373
10.1016/j.neuint.2017.02.016
10.1073/pnas.0905780106
10.3389/fnins.2011.00141
10.1093/hmg/ddt386
10.1124/jpet.115.226969
10.1007/s00018-013-1390-5
10.1093/hmg/10.19.2165
10.1038/nsmb.1958
10.1111/j.1365-2990.2009.01014.x
10.1038/ncomms3044
10.1016/S1097-2765(02)00563-4
10.1016/j.stem.2011.02.004
10.1021/cb3001606
10.1002/stem.1430
10.1021/ja210088v
10.1203/PDR.0b013e31822e1825
10.1073/pnas.1408964111
10.1016/j.ijcard.2012.03.109
10.1126/science.1088583
10.1038/nsmb.1720
10.1016/j.ccc.2012.07.005
10.1016/j.ebiom.2016.05.032
10.1002/acn3.271
10.1073/pnas.1117019109
10.1038/nature11362
10.1016/j.biocel.2010.08.010
10.1093/hmg/ddt542
10.1212/WNL.0b013e3181dc1a3a
10.1016/S0008-6363(96)00163-0
10.1073/pnas.0801661105
10.1038/nbt.2435
10.1126/science.1546325
10.1002/ana.23992
10.1111/febs.12448
10.1016/j.ijcard.2012.04.086
10.1016/j.drudis.2017.07.011
10.1038/ng704
10.1261/rna.032912.112
10.2353/ajpath.2009.080560
10.1172/JCI64081
10.2165/00129784-200707030-00004
10.1097/WCO.0000000000000128
10.1242/jcs.116285
ContentType Journal Article
Copyright 2018 The Author(s)
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
Distributed under a Creative Commons Attribution 4.0 International License
2018 The Author(s) 2018
Copyright_xml – notice: 2018 The Author(s)
– notice: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
– notice: Distributed under a Creative Commons Attribution 4.0 International License
– notice: 2018 The Author(s) 2018
DBID 6I.
AAFTH
AAYXX
CITATION
NPM
7X8
1XC
VOOES
5PM
DOA
DOI 10.1016/j.isci.2018.12.019
DatabaseName ScienceDirect Open Access Titles
Elsevier:ScienceDirect:Open Access
CrossRef
PubMed
MEDLINE - Academic
Hyper Article en Ligne (HAL)
Hyper Article en Ligne (HAL) (Open Access)
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
PubMed
MEDLINE - Academic
DatabaseTitleList
PubMed


MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
EISSN 2589-0042
EndPage 271
ExternalDocumentID oai_doaj_org_article_11e934f15b8347d3af89003142c3acd6
PMC6327858
oai_HAL_hal_01984689v1
30639849
10_1016_j_isci_2018_12_019
S2589004218302499
Genre Journal Article
GroupedDBID 0SF
53G
6I.
AACTN
AAEDW
AAFTH
AALRI
AAXUO
ABMAC
ADBBV
AEXQZ
AFTJW
AITUG
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
AOIJS
BCNDV
EBS
EJD
FDB
GROUPED_DOAJ
HYE
M41
NCXOZ
OK1
ROL
RPM
SSZ
0R~
AAMRU
AAYWO
AAYXX
ACVFH
ADCNI
ADVLN
AEUPX
AFPUW
AIGII
AKBMS
AKYEP
APXCP
CITATION
NPM
7X8
1XC
VOOES
5PM
ID FETCH-LOGICAL-c555t-cc0b13a539925d0318c4fa33786ae1e4d2ab561c40b81c9d68ae25458399afb33
IEDL.DBID DOA
ISSN 2589-0042
IngestDate Wed Aug 27 01:30:56 EDT 2025
Thu Aug 21 18:28:12 EDT 2025
Fri May 09 12:17:29 EDT 2025
Fri Jul 11 10:14:57 EDT 2025
Mon Jul 21 05:58:54 EDT 2025
Tue Jul 01 01:03:25 EDT 2025
Thu Apr 24 23:12:53 EDT 2025
Wed May 17 00:10:03 EDT 2023
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords Molecular Biology
Physiology
Cell Biology
Language English
License This is an open access article under the CC BY-NC-ND license.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c555t-cc0b13a539925d0318c4fa33786ae1e4d2ab561c40b81c9d68ae25458399afb33
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Lead Contact
ORCID 0000-0002-5234-1064
0000-0001-9519-2436
0000-0001-7912-4409
0000-0002-3757-0002
0000-0001-9966-3282
0000-0002-5601-3498
0000-0002-1617-4617
0009-0004-3349-1819
OpenAccessLink https://doaj.org/article/11e934f15b8347d3af89003142c3acd6
PMID 30639849
PQID 2179339646
PQPubID 23479
PageCount 14
ParticipantIDs doaj_primary_oai_doaj_org_article_11e934f15b8347d3af89003142c3acd6
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6327858
hal_primary_oai_HAL_hal_01984689v1
proquest_miscellaneous_2179339646
pubmed_primary_30639849
crossref_citationtrail_10_1016_j_isci_2018_12_019
crossref_primary_10_1016_j_isci_2018_12_019
elsevier_sciencedirect_doi_10_1016_j_isci_2018_12_019
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2019-01-25
PublicationDateYYYYMMDD 2019-01-25
PublicationDate_xml – month: 01
  year: 2019
  text: 2019-01-25
  day: 25
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle iScience
PublicationTitleAlternate iScience
PublicationYear 2019
Publisher Elsevier Inc
Elsevier
Publisher_xml – name: Elsevier Inc
– name: Elsevier
References Ueki, Nakamori, Nakamura, Nishikawa, Yoshida, Tanaka, Morizane, Kamon, Araki, Takahashi (bib50) 2017; 7
Dedkova, Sigova, Zinchenko (bib10) 2000; 13
Marteyn, Maury, Gauthier, Lecuyer, Vernet, Denis, Pietu, Peschanski, Martinat (bib33) 2011; 8
Konieczny, Selma-Soriano, Rapisarda, Fernandez-Costa, Perez-Alonso, Artero (bib24) 2017; 22
Sharma, Lou (bib44) 2011; 5
Finsterer, Stollberger (bib15) 2012; 160
Darville, Poulet, Rodet-Amsellem, Chatrousse, Pernelle, Boissart, Heron, Nava, Perrier, Jarrige (bib9) 2016; 9
Axelrod, Liebes, Gold-Von Simson, Mendoza, Mull, Leyne, Norcliffe-Kaufmann, Kaufmann, Slaugenhaupt (bib2) 2011; 70
Kanji, MacLean (bib22) 2012; 28
Farrelly-Rosch, Lau, Patil, Turner, Shabanpoor (bib14) 2017; 108
Pandey, Wheeler, Justice, Kim, Younis, Gattis, Jauvin, Puymirat, Swayze, Freier (bib37) 2015; 355
Chang, Liu, Yang, Lee, Lin, Chen, Chang (bib5) 2011; 71
Parkesh, Childs-Disney, Nakamori, Kumar, Wang, Wang, Hoskins, Tran, Housman, Thornton (bib38) 2012; 134
Bigot, Klein, Gasnier, Jacquemin, Ravassard, Butler-Browne, Mouly, Furling (bib4) 2009; 174
Lagoeiro Jorge, Lanzieri, Braida do Carmo, Haffner, Lagoeiro Jorge, Wolney de Andrade (bib25) 2012; 7
Gauthier, Marteyn, Denis, Cailleret, Giraud-Triboult, Aubert, Lecuyer, Marie, Furling, Vernet (bib18) 2013; 22
Phillips, Harper (bib39) 1997; 33
Fontana, Burlaka, Khodus, Brismar, Aperia (bib16) 2013; 280
Mahadevan, Tsilfidis, Sabourin, Shutler, Amemiya, Jansen, Neville, Narang, Barcelo, O'Hoy (bib30) 1992; 255
Sharma, Nguyen, Geng, Hinman, Luo, Lou (bib45) 2014; 111
Lee, Bennett, Cooper (bib28) 2012; 109
Laustriat, Gide, Barrault, Chautard, Benoit, Auboeuf, Boland, Battail, Artiguenave, Deleuze (bib26) 2015; 4
Logigian, Martens, Moxley, McDermott, Dilek, Wiegner, Pearson, Barbieri, Annis, Thornton (bib29) 2010; 74
Francois, Klein, Beley, Jollet, Lemercier, Garcia, Furling (bib17) 2011; 18
Wheeler, Leger, Pandey, MacLeod, Nakamori, Cheng, Wentworth, Bennett, Thornton (bib52) 2012; 488
Wheeler, Lueck, Swanson, Dirksen, Thornton (bib53) 2007; 117
Charbord, Poydenot, Bonnefond, Feyeux, Casagrande, Brinon, Francelle, Auregan, Guillermier, Cailleret (bib6) 2013; 31
Wei, Stock, Valanejad, Zalewski, Karns, Puymirat, Nelson, Witte, Woodgett, Timchenko (bib51) 2018; 32
Childs-Disney, Parkesh, Nakamori, Thornton, Disney (bib7) 2012; 7
Jones, Wei, Iakova, Bugiardini, Schneider-Gold, Meola, Woodgett, Killian, Timchenko, Timchenko (bib20) 2012; 122
Stoilov, Lin, Damoiseaux, Nikolic, Black (bib46) 2008; 105
Savkur, Philips, Cooper (bib41) 2001; 29
Nakamori, Sobczak, Puwanant, Welle, Eichinger, Pandya, Dekdebrun, Heatwole, McDermott, Chen (bib35) 2013; 74
Mankodi, Urbinati, Yuan, Moxley, Sansone, Krym, Henderson, Schalling, Swanson, Thornton (bib32) 2001; 10
Schmitt, Schmidt (bib42) 1975; 23
Du, Cline, Osborne, Tuttle, Clark, Donohue, Hall, Shiue, Swanson, Thornton (bib12) 2010; 17
Hothi, Chinnappa, Tan (bib19) 2014; 168
Anderson, Lin, Xiao, Stoilov, Burge, Black (bib1) 2012; 18
Razanau, Xie (bib40) 2013; 70
Schoner, Scheiner-Bobis (bib43) 2007; 7
Mankodi, Takahashi, Jiang, Beck, Bowers, Moxley, Cannon, Thornton (bib31) 2002; 10
Kanadia, Johnstone, Mankodi, Lungu, Thornton, Esson, Timmers, Hauswirth, Swanson (bib21) 2003; 302
Thornell, Lindstom, Renault, Klein, Mouly, Ansved, Butler-Browne, Furling (bib47) 2009; 35
Lee, Ramirez, Kim, Zeltner, Liu, Radu, Bhinder, Kim, Choi, Mukherjee-Clavin (bib27) 2012; 30
Mulders, van den Broek, Wheeler, Croes, van Kuik-Romeijn, de Kimpe, Furling, Platenburg, Gourdon, Thornton (bib34) 2009; 106
Nakamori, Taylor, Mochizuki, Sobczak, Takahashi (bib36) 2016; 3
Turner, Hilton-Jones (bib49) 2014; 27
Thornton, Wang, Carrell (bib48) 2017; 44
Ketley, Chen, Li, Arya, Robinson, Granados-Riveron, Udosen, Morris, Holt, Furling (bib23) 2013; 23
Beffy, Del Carratore, Masini, Furling, Puymirat, Masiello, Simili (bib3) 2010; 42
Denis, Gauthier, Rachdi, Aubert, Giraud-Triboult, Poydenot, Benchoua, Champon, Maury, Baldeschi (bib11) 2013; 126
Childs-Disney, Stepniak-Konieczna, Tran, Yildirim, Park, Chen, Hoskins, Southall, Marugan, Patnaik (bib8) 2013; 4
Du, Campau, Soragni, Jespersen, Gottesfeld (bib13) 2013; 22
Parkesh (10.1016/j.isci.2018.12.019_bib38) 2012; 134
Bigot (10.1016/j.isci.2018.12.019_bib4) 2009; 174
Pandey (10.1016/j.isci.2018.12.019_bib37) 2015; 355
Laustriat (10.1016/j.isci.2018.12.019_bib26) 2015; 4
Marteyn (10.1016/j.isci.2018.12.019_bib33) 2011; 8
Thornell (10.1016/j.isci.2018.12.019_bib47) 2009; 35
Wei (10.1016/j.isci.2018.12.019_bib51) 2018; 32
Lee (10.1016/j.isci.2018.12.019_bib27) 2012; 30
Sharma (10.1016/j.isci.2018.12.019_bib44) 2011; 5
Denis (10.1016/j.isci.2018.12.019_bib11) 2013; 126
Mahadevan (10.1016/j.isci.2018.12.019_bib30) 1992; 255
Phillips (10.1016/j.isci.2018.12.019_bib39) 1997; 33
Mulders (10.1016/j.isci.2018.12.019_bib34) 2009; 106
Farrelly-Rosch (10.1016/j.isci.2018.12.019_bib14) 2017; 108
Finsterer (10.1016/j.isci.2018.12.019_bib15) 2012; 160
Hothi (10.1016/j.isci.2018.12.019_bib19) 2014; 168
Gauthier (10.1016/j.isci.2018.12.019_bib18) 2013; 22
Jones (10.1016/j.isci.2018.12.019_bib20) 2012; 122
Francois (10.1016/j.isci.2018.12.019_bib17) 2011; 18
Kanadia (10.1016/j.isci.2018.12.019_bib21) 2003; 302
Ketley (10.1016/j.isci.2018.12.019_bib23) 2013; 23
Childs-Disney (10.1016/j.isci.2018.12.019_bib8) 2013; 4
Nakamori (10.1016/j.isci.2018.12.019_bib36) 2016; 3
Darville (10.1016/j.isci.2018.12.019_bib9) 2016; 9
Axelrod (10.1016/j.isci.2018.12.019_bib2) 2011; 70
Stoilov (10.1016/j.isci.2018.12.019_bib46) 2008; 105
Konieczny (10.1016/j.isci.2018.12.019_bib24) 2017; 22
Lagoeiro Jorge (10.1016/j.isci.2018.12.019_bib25) 2012; 7
Du (10.1016/j.isci.2018.12.019_bib12) 2010; 17
Lee (10.1016/j.isci.2018.12.019_bib28) 2012; 109
Dedkova (10.1016/j.isci.2018.12.019_bib10) 2000; 13
Ueki (10.1016/j.isci.2018.12.019_bib50) 2017; 7
Turner (10.1016/j.isci.2018.12.019_bib49) 2014; 27
Mankodi (10.1016/j.isci.2018.12.019_bib32) 2001; 10
Schoner (10.1016/j.isci.2018.12.019_bib43) 2007; 7
Beffy (10.1016/j.isci.2018.12.019_bib3) 2010; 42
Fontana (10.1016/j.isci.2018.12.019_bib16) 2013; 280
Anderson (10.1016/j.isci.2018.12.019_bib1) 2012; 18
Savkur (10.1016/j.isci.2018.12.019_bib41) 2001; 29
Mankodi (10.1016/j.isci.2018.12.019_bib31) 2002; 10
Logigian (10.1016/j.isci.2018.12.019_bib29) 2010; 74
Thornton (10.1016/j.isci.2018.12.019_bib48) 2017; 44
Nakamori (10.1016/j.isci.2018.12.019_bib35) 2013; 74
Childs-Disney (10.1016/j.isci.2018.12.019_bib7) 2012; 7
Sharma (10.1016/j.isci.2018.12.019_bib45) 2014; 111
Wheeler (10.1016/j.isci.2018.12.019_bib52) 2012; 488
Chang (10.1016/j.isci.2018.12.019_bib5) 2011; 71
Charbord (10.1016/j.isci.2018.12.019_bib6) 2013; 31
Razanau (10.1016/j.isci.2018.12.019_bib40) 2013; 70
Schmitt (10.1016/j.isci.2018.12.019_bib42) 1975; 23
Du (10.1016/j.isci.2018.12.019_bib13) 2013; 22
Kanji (10.1016/j.isci.2018.12.019_bib22) 2012; 28
Wheeler (10.1016/j.isci.2018.12.019_bib53) 2007; 117
References_xml – volume: 42
  start-page: 1973
  year: 2010
  end-page: 1983
  ident: bib3
  article-title: Altered signal transduction pathways and induction of autophagy in human myotonic dystrophy type 1 myoblasts
  publication-title: Int. J. Biochem. Cell Biol.
– volume: 18
  start-page: 85
  year: 2011
  end-page: 87
  ident: bib17
  article-title: Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs
  publication-title: Nat. Struct. Mol. Biol.
– volume: 122
  start-page: 4461
  year: 2012
  end-page: 4472
  ident: bib20
  article-title: GSK3beta mediates muscle pathology in myotonic dystrophy
  publication-title: J. Clin. Invest.
– volume: 280
  start-page: 5450
  year: 2013
  end-page: 5455
  ident: bib16
  article-title: Calcium oscillations triggered by cardiotonic steroids
  publication-title: FEBS J.
– volume: 255
  start-page: 1253
  year: 1992
  end-page: 1255
  ident: bib30
  article-title: Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene
  publication-title: Science
– volume: 9
  start-page: 293
  year: 2016
  end-page: 305
  ident: bib9
  article-title: Human pluripotent stem cell-derived cortical neurons for high throughput medication screening in autism: a proof of concept study in SHANK3 haploinsufficiency syndrome
  publication-title: EBioMedicine
– volume: 4
  start-page: 2044
  year: 2013
  ident: bib8
  article-title: Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules
  publication-title: Nat. Commun.
– volume: 29
  start-page: 40
  year: 2001
  end-page: 47
  ident: bib41
  article-title: Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
  publication-title: Nat. Genet.
– volume: 17
  start-page: 187
  year: 2010
  end-page: 193
  ident: bib12
  article-title: Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy
  publication-title: Nat. Struct. Mol. Biol.
– volume: 22
  start-page: 5188
  year: 2013
  end-page: 5198
  ident: bib18
  article-title: A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1
  publication-title: Hum. Mol. Genet.
– volume: 355
  start-page: 329
  year: 2015
  end-page: 340
  ident: bib37
  article-title: Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1
  publication-title: J. Pharmacol. Exp. Ther.
– volume: 7
  start-page: 1984
  year: 2012
  end-page: 1993
  ident: bib7
  article-title: Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1
  publication-title: ACS Chem. Biol.
– volume: 488
  start-page: 111
  year: 2012
  end-page: 115
  ident: bib52
  article-title: Targeting nuclear RNA for in vivo correction of myotonic dystrophy
  publication-title: Nature
– volume: 126
  start-page: 1763
  year: 2013
  end-page: 1772
  ident: bib11
  article-title: mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by myotonic dystrophy type 1
  publication-title: J. Cell Sci.
– volume: 168
  start-page: 645
  year: 2014
  end-page: 647
  ident: bib19
  article-title: 200+ years of a misunderstood drug for treating chronic heart failure: digoxin, why and how should we continue using it?
  publication-title: Int. J. Cardiol.
– volume: 22
  start-page: 5276
  year: 2013
  end-page: 5287
  ident: bib13
  article-title: Length-dependent CTG.CAG triplet-repeat expansion in myotonic dystrophy patient-derived induced pluripotent stem cells
  publication-title: Hum. Mol. Genet.
– volume: 18
  start-page: 1041
  year: 2012
  end-page: 1049
  ident: bib1
  article-title: Thecardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B
  publication-title: RNA
– volume: 134
  start-page: 4731
  year: 2012
  end-page: 4742
  ident: bib38
  article-title: Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching
  publication-title: J. Am. Chem. Soc.
– volume: 70
  start-page: 4527
  year: 2013
  end-page: 4536
  ident: bib40
  article-title: Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells
  publication-title: Cell.Mol. Life Sci.
– volume: 109
  start-page: 4221
  year: 2012
  end-page: 4226
  ident: bib28
  article-title: RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 105
  start-page: 11218
  year: 2008
  end-page: 11223
  ident: bib46
  article-title: A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 108
  start-page: 213
  year: 2017
  end-page: 221
  ident: bib14
  article-title: Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts
  publication-title: Neurochem.Int.
– volume: 30
  start-page: 1244
  year: 2012
  end-page: 1248
  ident: bib27
  article-title: Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression
  publication-title: Nat. Biotechnol.
– volume: 7
  start-page: 173
  year: 2007
  end-page: 189
  ident: bib43
  article-title: Endogenous and exogenous cardiac glycosides and their mechanisms of action
  publication-title: Am. J. Cardiovasc. Drugs
– volume: 23
  start-page: 1551
  year: 2013
  end-page: 1562
  ident: bib23
  article-title: High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines
  publication-title: Hum. Mol. Genet.
– volume: 32
  start-page: 2073
  year: 2018
  end-page: 2085
  ident: bib51
  article-title: Correction of GSK3beta at young age prevents muscle pathology in mice with myotonic dystrophy type 1
  publication-title: FASEB J.
– volume: 160
  start-page: e50
  year: 2012
  end-page: e51
  ident: bib15
  article-title: Beneficial effect of digitoxin for heart failure from noncompaction in myotonic dystrophy 1
  publication-title: Int. J. Cardiol.
– volume: 8
  start-page: 434
  year: 2011
  end-page: 444
  ident: bib33
  article-title: Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy
  publication-title: Cell Stem Cell
– volume: 3
  start-page: 42
  year: 2016
  end-page: 54
  ident: bib36
  article-title: Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy
  publication-title: Ann. Clin. Transl. Neurol.
– volume: 10
  start-page: 2165
  year: 2001
  end-page: 2170
  ident: bib32
  article-title: Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2
  publication-title: Hum. Mol. Genet.
– volume: 174
  start-page: 1435
  year: 2009
  end-page: 1442
  ident: bib4
  article-title: Large CTG repeats trigger p16-dependent premature senescence in myotonic dystrophy type 1 muscle precursor cells
  publication-title: Am. J. Pathol.
– volume: 4
  start-page: e262
  year: 2015
  ident: bib26
  article-title: In vitro and in vivo modulation of alternative splicing by the biguanide metformin
  publication-title: Mol. Ther. Nucleic Acids
– volume: 5
  start-page: 141
  year: 2011
  ident: bib44
  article-title: Depolarization-mediated regulation of alternative splicing
  publication-title: Front. Neurosci.
– volume: 35
  start-page: 603
  year: 2009
  end-page: 613
  ident: bib47
  article-title: Satellite cell dysfunction contributes to the progressive muscle atrophy in myotonic dystrophy type 1
  publication-title: Neuropathol. Appl. Neurobiol.
– volume: 106
  start-page: 13915
  year: 2009
  end-page: 13920
  ident: bib34
  article-title: Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 13
  start-page: 357
  year: 2000
  end-page: 368
  ident: bib10
  article-title: Mechanism of action of calcium ionophores on intact cells: ionophore-resistant cells
  publication-title: Membr.Cell Biol.
– volume: 74
  start-page: 1441
  year: 2010
  end-page: 1448
  ident: bib29
  article-title: Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1
  publication-title: Neurology
– volume: 74
  start-page: 862
  year: 2013
  end-page: 872
  ident: bib35
  article-title: Splicing biomarkers of disease severity in myotonic dystrophy
  publication-title: Ann. Neurol.
– volume: 7
  start-page: 42522
  year: 2017
  ident: bib50
  article-title: Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability
  publication-title: Sci. Rep.
– volume: 44
  start-page: 135
  year: 2017
  end-page: 140
  ident: bib48
  article-title: Myotonic dystrophy: approach to therapy
  publication-title: Curr.Opin.Genet. Dev.
– volume: 28
  start-page: 527
  year: 2012
  end-page: 535
  ident: bib22
  article-title: Cardiac glycoside toxicity: more than 200 years and counting
  publication-title: Crit. Care Clin.
– volume: 111
  start-page: E4920
  year: 2014
  end-page: E4928
  ident: bib45
  article-title: Calcium-mediated histone modifications regulate alternative splicing in cardyomyocytes
  publication-title: Proc. Natl. Acad. Sci. U S A
– volume: 7
  start-page: 143
  year: 2012
  end-page: 147
  ident: bib25
  article-title: Cardiomyopathy secondary to Steinert’s dystrophy
  publication-title: Insuficiencia Cardiaca
– volume: 70
  start-page: 480
  year: 2011
  end-page: 483
  ident: bib2
  article-title: Kinetin improves IKBKAP mRNA splicing in patients with familial dysautonomia
  publication-title: Pediatr. Res.
– volume: 27
  start-page: 599
  year: 2014
  end-page: 606
  ident: bib49
  article-title: Myotonic dystrophy: diagnosis, management and new therapies
  publication-title: Curr.Opin. Neurol.
– volume: 22
  start-page: 1740
  year: 2017
  end-page: 1748
  ident: bib24
  article-title: Myotonicdystrophy: candidate small molecule therapeutics
  publication-title: Drug Discov. Today
– volume: 117
  start-page: 3952
  year: 2007
  end-page: 3957
  ident: bib53
  article-title: Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy
  publication-title: J. Clin. Invest.
– volume: 302
  start-page: 1978
  year: 2003
  end-page: 1980
  ident: bib21
  article-title: A muscleblind knockout model for myotonic dystrophy
  publication-title: Science
– volume: 31
  start-page: 1816
  year: 2013
  end-page: 1828
  ident: bib6
  article-title: High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes
  publication-title: Stem Cells
– volume: 71
  start-page: 383
  year: 2011
  end-page: 392
  ident: bib5
  article-title: Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib
  publication-title: Cancer Res.
– volume: 10
  start-page: 35
  year: 2002
  end-page: 44
  ident: bib31
  article-title: Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
  publication-title: Mol. Cell
– volume: 33
  start-page: 13
  year: 1997
  end-page: 22
  ident: bib39
  article-title: Cardiac disease in myotonic dystrophy
  publication-title: Cardiovasc. Res.
– volume: 23
  start-page: 59
  year: 1975
  end-page: 64
  ident: bib42
  article-title: [Steinert's syndrome and the myocardium. Total gene expression by the myocardium]
  publication-title: J. Genet. Hum.
– volume: 32
  start-page: 2073
  year: 2018
  ident: 10.1016/j.isci.2018.12.019_bib51
  article-title: Correction of GSK3beta at young age prevents muscle pathology in mice with myotonic dystrophy type 1
  publication-title: FASEB J.
  doi: 10.1096/fj.201700700R
– volume: 71
  start-page: 383
  year: 2011
  ident: 10.1016/j.isci.2018.12.019_bib5
  article-title: Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-10-1037
– volume: 4
  start-page: e262
  year: 2015
  ident: 10.1016/j.isci.2018.12.019_bib26
  article-title: In vitro and in vivo modulation of alternative splicing by the biguanide metformin
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1038/mtna.2015.35
– volume: 44
  start-page: 135
  year: 2017
  ident: 10.1016/j.isci.2018.12.019_bib48
  article-title: Myotonic dystrophy: approach to therapy
  publication-title: Curr.Opin.Genet. Dev.
  doi: 10.1016/j.gde.2017.03.007
– volume: 7
  start-page: 42522
  year: 2017
  ident: 10.1016/j.isci.2018.12.019_bib50
  article-title: Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability
  publication-title: Sci. Rep.
  doi: 10.1038/srep42522
– volume: 22
  start-page: 5188
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib18
  article-title: A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/ddt373
– volume: 108
  start-page: 213
  year: 2017
  ident: 10.1016/j.isci.2018.12.019_bib14
  article-title: Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts
  publication-title: Neurochem.Int.
  doi: 10.1016/j.neuint.2017.02.016
– volume: 106
  start-page: 13915
  year: 2009
  ident: 10.1016/j.isci.2018.12.019_bib34
  article-title: Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.0905780106
– volume: 5
  start-page: 141
  year: 2011
  ident: 10.1016/j.isci.2018.12.019_bib44
  article-title: Depolarization-mediated regulation of alternative splicing
  publication-title: Front. Neurosci.
  doi: 10.3389/fnins.2011.00141
– volume: 22
  start-page: 5276
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib13
  article-title: Length-dependent CTG.CAG triplet-repeat expansion in myotonic dystrophy patient-derived induced pluripotent stem cells
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/ddt386
– volume: 355
  start-page: 329
  year: 2015
  ident: 10.1016/j.isci.2018.12.019_bib37
  article-title: Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1
  publication-title: J. Pharmacol. Exp. Ther.
  doi: 10.1124/jpet.115.226969
– volume: 117
  start-page: 3952
  year: 2007
  ident: 10.1016/j.isci.2018.12.019_bib53
  article-title: Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy
  publication-title: J. Clin. Invest.
– volume: 70
  start-page: 4527
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib40
  article-title: Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells
  publication-title: Cell.Mol. Life Sci.
  doi: 10.1007/s00018-013-1390-5
– volume: 10
  start-page: 2165
  year: 2001
  ident: 10.1016/j.isci.2018.12.019_bib32
  article-title: Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/10.19.2165
– volume: 18
  start-page: 85
  year: 2011
  ident: 10.1016/j.isci.2018.12.019_bib17
  article-title: Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs
  publication-title: Nat. Struct. Mol. Biol.
  doi: 10.1038/nsmb.1958
– volume: 35
  start-page: 603
  year: 2009
  ident: 10.1016/j.isci.2018.12.019_bib47
  article-title: Satellite cell dysfunction contributes to the progressive muscle atrophy in myotonic dystrophy type 1
  publication-title: Neuropathol. Appl. Neurobiol.
  doi: 10.1111/j.1365-2990.2009.01014.x
– volume: 4
  start-page: 2044
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib8
  article-title: Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms3044
– volume: 10
  start-page: 35
  year: 2002
  ident: 10.1016/j.isci.2018.12.019_bib31
  article-title: Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
  publication-title: Mol. Cell
  doi: 10.1016/S1097-2765(02)00563-4
– volume: 8
  start-page: 434
  year: 2011
  ident: 10.1016/j.isci.2018.12.019_bib33
  article-title: Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2011.02.004
– volume: 7
  start-page: 1984
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib7
  article-title: Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1
  publication-title: ACS Chem. Biol.
  doi: 10.1021/cb3001606
– volume: 31
  start-page: 1816
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib6
  article-title: High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes
  publication-title: Stem Cells
  doi: 10.1002/stem.1430
– volume: 134
  start-page: 4731
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib38
  article-title: Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching
  publication-title: J. Am. Chem. Soc.
  doi: 10.1021/ja210088v
– volume: 70
  start-page: 480
  year: 2011
  ident: 10.1016/j.isci.2018.12.019_bib2
  article-title: Kinetin improves IKBKAP mRNA splicing in patients with familial dysautonomia
  publication-title: Pediatr. Res.
  doi: 10.1203/PDR.0b013e31822e1825
– volume: 111
  start-page: E4920
  year: 2014
  ident: 10.1016/j.isci.2018.12.019_bib45
  article-title: Calcium-mediated histone modifications regulate alternative splicing in cardyomyocytes
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.1408964111
– volume: 160
  start-page: e50
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib15
  article-title: Beneficial effect of digitoxin for heart failure from noncompaction in myotonic dystrophy 1
  publication-title: Int. J. Cardiol.
  doi: 10.1016/j.ijcard.2012.03.109
– volume: 302
  start-page: 1978
  year: 2003
  ident: 10.1016/j.isci.2018.12.019_bib21
  article-title: A muscleblind knockout model for myotonic dystrophy
  publication-title: Science
  doi: 10.1126/science.1088583
– volume: 17
  start-page: 187
  year: 2010
  ident: 10.1016/j.isci.2018.12.019_bib12
  article-title: Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy
  publication-title: Nat. Struct. Mol. Biol.
  doi: 10.1038/nsmb.1720
– volume: 23
  start-page: 59
  year: 1975
  ident: 10.1016/j.isci.2018.12.019_bib42
  article-title: [Steinert's syndrome and the myocardium. Total gene expression by the myocardium]
  publication-title: J. Genet. Hum.
– volume: 28
  start-page: 527
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib22
  article-title: Cardiac glycoside toxicity: more than 200 years and counting
  publication-title: Crit. Care Clin.
  doi: 10.1016/j.ccc.2012.07.005
– volume: 9
  start-page: 293
  year: 2016
  ident: 10.1016/j.isci.2018.12.019_bib9
  article-title: Human pluripotent stem cell-derived cortical neurons for high throughput medication screening in autism: a proof of concept study in SHANK3 haploinsufficiency syndrome
  publication-title: EBioMedicine
  doi: 10.1016/j.ebiom.2016.05.032
– volume: 13
  start-page: 357
  year: 2000
  ident: 10.1016/j.isci.2018.12.019_bib10
  article-title: Mechanism of action of calcium ionophores on intact cells: ionophore-resistant cells
  publication-title: Membr.Cell Biol.
– volume: 3
  start-page: 42
  year: 2016
  ident: 10.1016/j.isci.2018.12.019_bib36
  article-title: Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy
  publication-title: Ann. Clin. Transl. Neurol.
  doi: 10.1002/acn3.271
– volume: 109
  start-page: 4221
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib28
  article-title: RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.1117019109
– volume: 488
  start-page: 111
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib52
  article-title: Targeting nuclear RNA for in vivo correction of myotonic dystrophy
  publication-title: Nature
  doi: 10.1038/nature11362
– volume: 42
  start-page: 1973
  year: 2010
  ident: 10.1016/j.isci.2018.12.019_bib3
  article-title: Altered signal transduction pathways and induction of autophagy in human myotonic dystrophy type 1 myoblasts
  publication-title: Int. J. Biochem. Cell Biol.
  doi: 10.1016/j.biocel.2010.08.010
– volume: 23
  start-page: 1551
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib23
  article-title: High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/ddt542
– volume: 74
  start-page: 1441
  year: 2010
  ident: 10.1016/j.isci.2018.12.019_bib29
  article-title: Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1
  publication-title: Neurology
  doi: 10.1212/WNL.0b013e3181dc1a3a
– volume: 33
  start-page: 13
  year: 1997
  ident: 10.1016/j.isci.2018.12.019_bib39
  article-title: Cardiac disease in myotonic dystrophy
  publication-title: Cardiovasc. Res.
  doi: 10.1016/S0008-6363(96)00163-0
– volume: 105
  start-page: 11218
  year: 2008
  ident: 10.1016/j.isci.2018.12.019_bib46
  article-title: A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators
  publication-title: Proc. Natl. Acad. Sci. U S A
  doi: 10.1073/pnas.0801661105
– volume: 30
  start-page: 1244
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib27
  article-title: Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.2435
– volume: 255
  start-page: 1253
  year: 1992
  ident: 10.1016/j.isci.2018.12.019_bib30
  article-title: Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene
  publication-title: Science
  doi: 10.1126/science.1546325
– volume: 74
  start-page: 862
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib35
  article-title: Splicing biomarkers of disease severity in myotonic dystrophy
  publication-title: Ann. Neurol.
  doi: 10.1002/ana.23992
– volume: 280
  start-page: 5450
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib16
  article-title: Calcium oscillations triggered by cardiotonic steroids
  publication-title: FEBS J.
  doi: 10.1111/febs.12448
– volume: 168
  start-page: 645
  year: 2014
  ident: 10.1016/j.isci.2018.12.019_bib19
  article-title: 200+ years of a misunderstood drug for treating chronic heart failure: digoxin, why and how should we continue using it?
  publication-title: Int. J. Cardiol.
  doi: 10.1016/j.ijcard.2012.04.086
– volume: 22
  start-page: 1740
  year: 2017
  ident: 10.1016/j.isci.2018.12.019_bib24
  article-title: Myotonicdystrophy: candidate small molecule therapeutics
  publication-title: Drug Discov. Today
  doi: 10.1016/j.drudis.2017.07.011
– volume: 29
  start-page: 40
  year: 2001
  ident: 10.1016/j.isci.2018.12.019_bib41
  article-title: Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
  publication-title: Nat. Genet.
  doi: 10.1038/ng704
– volume: 18
  start-page: 1041
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib1
  article-title: Thecardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B
  publication-title: RNA
  doi: 10.1261/rna.032912.112
– volume: 174
  start-page: 1435
  year: 2009
  ident: 10.1016/j.isci.2018.12.019_bib4
  article-title: Large CTG repeats trigger p16-dependent premature senescence in myotonic dystrophy type 1 muscle precursor cells
  publication-title: Am. J. Pathol.
  doi: 10.2353/ajpath.2009.080560
– volume: 122
  start-page: 4461
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib20
  article-title: GSK3beta mediates muscle pathology in myotonic dystrophy
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI64081
– volume: 7
  start-page: 173
  year: 2007
  ident: 10.1016/j.isci.2018.12.019_bib43
  article-title: Endogenous and exogenous cardiac glycosides and their mechanisms of action
  publication-title: Am. J. Cardiovasc. Drugs
  doi: 10.2165/00129784-200707030-00004
– volume: 7
  start-page: 143
  year: 2012
  ident: 10.1016/j.isci.2018.12.019_bib25
  article-title: Cardiomyopathy secondary to Steinert’s dystrophy
  publication-title: Insuficiencia Cardiaca
– volume: 27
  start-page: 599
  year: 2014
  ident: 10.1016/j.isci.2018.12.019_bib49
  article-title: Myotonic dystrophy: diagnosis, management and new therapies
  publication-title: Curr.Opin. Neurol.
  doi: 10.1097/WCO.0000000000000128
– volume: 126
  start-page: 1763
  year: 2013
  ident: 10.1016/j.isci.2018.12.019_bib11
  article-title: mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by myotonic dystrophy type 1
  publication-title: J. Cell Sci.
  doi: 10.1242/jcs.116285
SSID ssj0002002496
Score 2.106894
Snippet There is currently no treatment for myotonic dystrophy type 1 (DM1), the most frequent myopathy of genetic origin. This progressive neuromuscular disease is...
SourceID doaj
pubmedcentral
hal
proquest
pubmed
crossref
elsevier
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 258
SubjectTerms Cell Biology
Life Sciences
Molecular Biology
Pharmaceutical sciences
Pharmacology
Physiology
Title Pluripotent Stem Cell-Based Drug Screening Reveals Cardiac Glycosides as Modulators of Myotonic Dystrophy Type 1
URI https://dx.doi.org/10.1016/j.isci.2018.12.019
https://www.ncbi.nlm.nih.gov/pubmed/30639849
https://www.proquest.com/docview/2179339646
https://hal.sorbonne-universite.fr/hal-01984689
https://pubmed.ncbi.nlm.nih.gov/PMC6327858
https://doaj.org/article/11e934f15b8347d3af89003142c3acd6
Volume 11
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nb9QwELWgJy4IxFf4kkHcUMTajmPn2G4pK8QiRKnUm-XYDm0VkmqTrbT_nhknu9qAVC5c48ROPM-ZZ3v8hpB3HryIsnmWilBYmKBYluqscKmS3ilWOqUcHk5efs0XZ9nnc3m-l-oLY8IGeeCh4z4wFgqRVUyWWmTKC1tpXHxjGXfCOh_FtsHn7U2mruL2GkrhxcxyEmOCAJrjiZkhuAtPvGJcl45rgSizs-eVonj_xDndvcAoyb8p6J-RlHuu6eQBuT9ySno4fMtDcic0j8j1t3oNP4QWOHFPT_vwi85DXadH4LU8PV6tf9JThzE34Lro93ADfLGj8wgXRz_VG9diHs-O2o4uW485vtpVR9uKLjdtj3K69HjT9asWrERxLkvZY3J28vHHfJGO6RVSJ6XsU-dmJRM2StNKj4PbZZUVQuncBhYyz20J7Mpls1IzV_hc28Bxnw0esFUpxBNy0LRNeEaoLipfAXHMFQevONNFKcMMzMRdbjmwhISwbfcaN2qPYwqM2myDzK4MmsSgSQzjBkySkPe7Z64H5Y1b7z5Cq-3uRNXseAGwZEYsmX9hKSFya3MzEpCBWEBVl7c2_hYAMml7cfjF4DUoBYanixuWkDdb_BgYwrgvY5vQrjvD8ScpijyDF3g64GlXl0AKCaMnIWqCtElj05Lm8iLKhOeCKy318__RMy_IPfhejKxLuXxJDvrVOrwCNtaXr-PA-w2szC6Q
linkProvider Directory of Open Access Journals
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pluripotent+Stem+Cell-Based+Drug+Screening+Reveals+Cardiac+Glycosides+as+Modulators+of+Myotonic+Dystrophy+Type+1&rft.jtitle=iScience&rft.au=Maury%2C+Yves&rft.au=Poydenot%2C+Pauline&rft.au=Brinon%2C+Benjamin&rft.au=Lesueur%2C+Lea&rft.date=2019-01-25&rft.issn=2589-0042&rft.eissn=2589-0042&rft.volume=11&rft.spage=258&rft_id=info:doi/10.1016%2Fj.isci.2018.12.019&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2589-0042&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2589-0042&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2589-0042&client=summon