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Cited by 5Cardiovascular Effects of ExerciseCardiomyopathy and Myosin StudiesCardiac electrophysiology and arrhythmias

Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy

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Malhotra, Nipun, Cavus, Omer, Wallace, Michael J., Bobik, John T., You, Kevin, Takenaka, Sarah S., Abdallah, Danielle, Mohler, Eleanor J. +9 more·2025·JACC: Basic to Translational Science
DOI 10.1016/j.jacbts.2025.03.013PMC PMC12399120
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Abstract

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease, and current pharmacological therapies are directed toward the management of electrical manifestations. To date, none address the underlying pathophysiology of this progressive condition. We evaluated the therapeutic efficacy of Tideglusib (TD) in Ank2 cardio-selective-knockout and homozygous desmoglein-2 mutant ACM mouse models. TD was able to prevent and reverse the reduced cardiac function in treated mice. Moreover, TD-treated adult mice displayed a reduction in ventricular arrhythmia following adrenergic stimulation. We provide compelling preclinical data for TD as a potential therapy for patients with ACM.

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  • Tideglusib has shown promise in experimental settings and is currently being tested in a Phase 2 trial (NCT06174220).

    “Tideglusib, a repurposed GSK3β inhibitor, has shown promise in experimental settings and is currently being tested in a Phase 2 trial (NCT06174220) [76].”

    From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [76]

    The paper’s opening passage reports promising effects of tideglusib in two mouse models of arrhythmogenic cardiomyopathy and says those findings motivated a randomized controlled trial, NCT06174220. The Conclusions also identify that trial, but neither passage calls it Phase 2; the source therefore does not support the claimed trial phase. (LLM, conf=0.88)

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  • Targeting specific mediators within these pathways, whether through GSK3β inhibition (e.g., Tideglusib) or NFκB inhibition, restores cardiac function and attenuates disease-associated remodeling in experimental models of ACM.

    “Targeting specific mediators within these pathways, whether through GSK3β inhibition (e.g., Tideglusib) [76] or NFκB inhibition, has been shown to restore cardiac function and attenuate disease-associated remodeling in experimental models of ACM, further supporting mediators of inflammation as therapeutic targets.”

    From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [76]

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  1. [1]Stevens T.L. Wallace M.J. Refaey M.E. Roberts J.D. Koenig S.N. Mohler P.J. Arrhythmogenic cardiomyopathy: molecular insights for improved therapeutic design J Cardiovasc Dev Dis 7 2 2020 21 32466575 PMC7345706
  2. [2]Frank R. Fontaine G. Vedel J. [Electrocardiology of 4 cases of right ventricular dysplasia inducing arrhythmia] Archives des maladies du coeur et des vaisseaux 71 1978 963 972 102297
  3. [3]Dungan W.T. Garson A. Jr. Gillette P.C. Arrhythmogenic right ventricular dysplasia: a cause of ventricular tachycardia in children with apparently normal hearts Am Heart J 102 1981 745 750 7282521
  4. [4]Marcus F.I. McKenna W.J. Sherrill D. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia proposed modification of the task force criteria Circulation 121 2010 1533-U118 PMC2860804 20172911
  5. [5]Corrado D. Perazzolo Marra M. Zorzi A. Diagnosis of arrhythmogenic cardiomyopathy: the Padua criteria Int J Cardiol 319 2020 106 114 32561223
  6. [6]McKoy G. Protonotarios N. Crosby A. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease) Lancet 355 2000 2119 2124 10902626
  7. [7]Gerull B. Heuser A. Wichter T. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy Nat Genet 36 2004 1162 1164 15489853
  8. [8]Pilichou K. Nava A. Basso C. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy Circulation 113 2006 1171 1179 16505173
  9. [9]Syrris P. Ward D. Evans A. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2 Am J Hum Genet 79 2006 978 984 17033975 PMC1698574
  10. [10]Roberts J.D. Murphy N.P. Hamilton R.M. Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy J Clin Invest 129 2019 3171 3184 31264976 PMC6668697
  11. [11]Asimaki A. Kapoor S. Plovie E. Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy Sci Transl Med 6 2014 240ra74 PMC4471875 24920660
  12. [14]Padron-Barthe L. Villalba-Orero M. Gomez-Salinero J.M. Severe cardiac dysfunction and death caused by arrhythmogenic right ventricular cardiomyopathy type 5 are improved by inhibition of glycogen synthase kinase-3beta Circulation 140 2019 1188 1204 31567019 PMC6784777
  13. [15]Luna-Medina R. Cortes-Canteli M. Sanchez-Galiano S. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders J Neurosci 27 2007 5766 5776 17522320 PMC6672766
  14. [17]Siafis S. Ciray O. Wu H. Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis Mol Autism 13 2022 10 35246237 PMC8896153
  15. [18]Horrigan J. Gomes T.B. Snape M. A phase 2 study of AMO-02 (Tideglusib) in congenital and childhood-onset myotonic dystrophy type 1 (DM1) Pediatr Neurol 112 2020 84 93 32942085
  16. [19]Chelko S.P. Penna V.R. Engel M. NFkB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy J Clin Invest 134 13 2024 Jul 1 e183441 PMC11213461 38949031
  17. [20]Wallace M.J. Malhotra N. Mariangelo J.I.E. Impact of stress on cardiac phenotypes in mice harboring an ankyrin-B disease variant J Biol Chem 299 2023 104818 PMC10318515 37182735
  18. [21]Corrado D. Basso C. Judge D.P. Arrhythmogenic cardiomyopathy Circ Res 121 2017 784 802 28912183
  19. [22]Thiene G. Nava A. Corrado D. Rossi L. Pennelli N. Right ventricular cardiomyopathy and sudden death in young people N Engl J Med 318 1988 129 133 3336399
  20. [23]Nava A. Bauce B. Basso C. Clinical profile and long-term follow-up of 37 families with arrhythmogenic right ventricular cardiomyopathy J Am Coll Cardiol 36 2000 2226 2233 11127465
  21. [24]Lemola K. Brunckhorst C. Helfenstein U. Oechslin E. Jenni R. Duru F. Predictors of adverse outcome in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy: long term experience of a tertiary care centre Heart 91 2005 1167 1172 16103549 PMC1769099
  22. [25]Garcia-Gras E. Lombardi R. Giocondo M.J. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy J Clin Invest 116 2006 2012 2021 16823493 PMC1483165
  23. [26]Corrado D. Wichter T. Link M.S. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement Circulation 132 2015 441 453 26216213 PMC4521905
  24. [27]Corrado D. Basso C. Pavei A. Michieli P. Schiavon M. Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program JAMA 296 2006 1593 1601 17018804
  25. [28]Basso C. Corrado D. Marcus F.I. Nava A. Thiene G. Arrhythmogenic right ventricular cardiomyopathy Lancet 373 2009 1289 1300 19362677
  26. [29]Asimaki A. Tandri H. Huang H. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy N Engl J Med 360 2009 1075 1084 19279339
  27. [30]Krahn A.D. Wilde A.A.M. Calkins H. Arrhythmogenic right ventricular cardiomyopathy JACC Clin Electrophysiol 8 2022 533 553 35450611
  28. [31]Miles C. Finocchiaro G. Papadakis M. Sudden death and left ventricular involvement in arrhythmogenic cardiomyopathy Circulation 139 2019 1786 1797 30700137 PMC6467560
  29. [32]Towbin J.A. McKenna W.J. Abrams D.J. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary Heart Rhythm 16 2019 e373 e407 31676023
  30. [33]Palomo V. Perez D.I. Roca C. Subtly modulating glycogen synthase kinase 3 beta: allosteric inhibitor development and their potential for the treatment of chronic diseases J Med Chem 60 2017 4983 5001 28548834

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Authors
Malhotra, N., Cavus, O., Wallace, M. J., Bobik, J. T., You, K., Takenaka, S. S., Abdallah, D., Mohler, E. J., Antwi-Boasiako, S., Murphy, N. P., Sucharski-Argall, H., Xu, X., Chelko, S. P., Hund, T. J., Roberts, J. D., Mohler, P. J., & El Refaey, M.
Affiliations
  • The Ohio State University Wexner Medical Center (US)
  • Florida State University (US)
  • Population Health Research Institute (CA)
Corresponding author
  • Malhotra, Nipun
  • Cavus, Omer
ORCID
Venue
JACC: Basic to Translational Science
Publisher
Elsevier BV
Published
2025-08
Volume
10
Issue
8
Pages
101281
ISSN
2452-302X (ISSN-L)
DOI
10.1016/j.jacbts.2025.03.013
PMC
PMC12399120
OpenAlex
W4413564876
Cited by
5
References
3
Citations by year
2026: 3 · 2025: 2
FWCI
3.49
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC Basic to Translational Science (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Heart Lung and Blood Institute
  • Ohio State University
  • Fondation Leducq
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
tideglusib, arrhythmogenic cardiomyopathy, disease-modifying therapy, cardiac function, ventricular arrhythmias, adrenergic stimulation, inherited heart disease, GSK3 inhibition

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