Abstract
Original language | English |
---|---|
Pages (from-to) | 406-420 |
Number of pages | 15 |
Journal | European journal of heart failure |
Volume | 24 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Mar 2022 |
Keywords
- Cardiomyopathy
- Dilated cardiomyopathy
- Disease mechanism
- Gene therapy
- Heart failure
- Hypertrophic cardiomyopathy
- Molecular biology
- Pharmacology
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In: European journal of heart failure, Vol. 24, No. 3, 01.03.2022, p. 406-420.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Targeted therapies in genetic dilated and hypertrophic cardiomyopathies
T2 - from molecular mechanisms to therapeutic targets. A position paper from the Heart Failure Association (HFA) and the Working Group on Myocardial Function of the European Society of Cardiology (ESC)
AU - de Boer, Rudolf A.
AU - Heymans, Stephane
AU - Backs, Johannes
AU - Carrier, Lucie
AU - Coats, Andrew J. S.
AU - Dimmeler, Stefanie
AU - Eschenhagen, Thomas
AU - Filippatos, Gerasimos
AU - Gepstein, Lior
AU - Hulot, Jean-Sebastien
AU - Knöll, Ralph
AU - Kupatt, Christian
AU - Linke, Wolfgang A.
AU - Seidman, Christine E.
AU - Tocchetti, C. Gabriele
AU - van der Velden, Jolanda
AU - Walsh, Roddy
AU - Seferovic, Petar M.
AU - Thum, Thomas
N1 - Funding Information: Prof. de Boer is supported by grants from the Dutch Heart Foundation (CVON SHE‐PREDICTS‐HF, grant 2017‐21; CVON RED‐CVD, grant 2017‐11; CVON PREDICT2, grant 2018‐30; and DCVA DOUBLE‐DOSE, grant 2020B005), by a grant from the Leducq Foundation (Cure PhosphoLambaN‐induced cardiomyopathy; Cure‐PLaN), and by a grant from the European Research Council (ERC CoG 818715, SECRETE‐HF). Prof. Hulot is supported by grants from the French National Research Agency (NADHeart ANR‐17‐CE17‐0015‐02; PACIFIC ANR‐18‐CE14‐0032‐01; and CORRECT_LMNA ANR‐19‐CE17‐0013‐02), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale (EQU201903007852), a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure), and by a grant from the Leducq Foundation (18CVD05). Dr. Knöll is supported by grants from AstraZeneca, Hjärt och Lungfonden, and Deutsche Forschungsgemeinschaft (DFG). Prof. Kupatt is supported by the German Research Foundation (DFG SFB‐TRR127‐A2, SFB‐TRR 267‐B8) and the German Center for Cardiovascular Research (DZHK). Prof. Linke is funded by grants from the German Research Foundation (SFB1002‐TPA08) and the IZKF Muenster (Li1/029/20). Prof. van der Velden acknowledges support from NWO‐ZonMW (91818602 VICI grant), ZonMW and Heart Foundation for the translational research program, project 95105003; the Dutch Cardiovascular Alliance (DCVA) grant Double Dose 2021; and the Leducq Foundation grant number 20CVD01. Prof. Thum is supported by the EU (Grant Cardioregenix, GA 825670), the Deutsche Forschungsgemeinschaft DFG (TH903/20‐2 and INST 95/15641). Funding Information: The UMCG, which employs Prof. de Boer, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. S.H. received personal fees for scientific advice from AstraZeneca, CSL Behring, Cellprothera, Bayer and Merck; and an unrestricted research grant from Pfizer. A.J.S.C. declares no conflicts related to this work. Outside of this work, in the last 3 years, he declares having received honoraria and/or lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Menarini, Novartis, Nutricia, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Gore, Impulse Dynamics and Respicardia. S.D. holds patents on microRNA therapeutics. T.E. and L.C. hold a patent on gene‐therapy vectors for treating cardiomyopathy that was licensed to DiNAQOR AG, are members of the DiNAQOR Scientific Advisory Board, and have shares in DiNAQOR. The APHP, which employs Prof. Hulot, has received research grants from Bioserenity, Sanofi, Servier and Novo Nordisk. Outside of this work, J.S.H. has received speaker, advisory board or consultancy fees from Amgen, AstraZeneca, Bayer, Bioserenity, Boehringer Ingelheim, Bristol‐Myers Squibb, MSD, Novartis and Novo Nordisk. R.K. is an employee of AstraZeneca. C.K. holds a patent on AAV‐based gene editing for Duchenne muscular dystrophy and has received advisor or speaker fees from AstraZeneca and AskBio. C.E.S. is a founder of Myokardia (a Bristol‐Myers‐Squibb Subsidiary); a consultant of Maze and BridgeBio; and is member of the Board of Directors at Merck. C.G.T. has received funding from Amgen and personal fees from Vivalyfe, outside of the submitted work, and is listed as an inventor on two heart failure patents. Prof. Seferovic declares consulting fees for Boehringer Ingelheim, Novartis, Vifor Pharma; and honoraria for lectures for Servier, AstraZeneca, Respicardia, Boehringer Ingelheim, and Novartis. T.T. has filed and licensed patents in the field of noncoding RNAs; he is founder and shareholder of Cardior Pharmaceuticals GmbH and is on the advisory board and/or received speaker fees from Novo Nordisk, Boehringer Ingelheim, Takeda, Amicus Therapeutics, Ksilink and Sanofi‐Genzyme. Conflict of interest: Funding Information: Prof. de Boer is supported by grants from the Dutch Heart Foundation (CVON SHE-PREDICTS-HF, grant 2017-21; CVON RED-CVD, grant 2017-11; CVON PREDICT2, grant 2018-30; and DCVA DOUBLE-DOSE, grant 2020B005), by a grant from the Leducq Foundation (Cure PhosphoLambaN-induced cardiomyopathy; Cure-PLaN), and by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF). Prof. Hulot is supported by grants from the French National Research Agency (NADHeart ANR-17-CE17-0015-02; PACIFIC ANR-18-CE14-0032-01; and CORRECT_LMNA ANR-19-CE17-0013-02), F?d?ration Fran?aise de Cardiologie, the Fondation pour la Recherche M?dicale (EQU201903007852), a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure), and by a grant from the Leducq Foundation (18CVD05). Dr. Kn?ll is supported by grants from AstraZeneca, Hj?rt och Lungfonden, and Deutsche Forschungsgemeinschaft (DFG). Prof. Kupatt is supported by the German Research Foundation (DFG SFB-TRR127-A2, SFB-TRR 267-B8) and the German Center for Cardiovascular Research (DZHK). Prof. Linke is funded by grants from the German Research Foundation (SFB1002-TPA08) and the IZKF Muenster (Li1/029/20). Prof. van der Velden acknowledges support from NWO-ZonMW (91818602 VICI grant), ZonMW and Heart Foundation for the translational research program, project 95105003; the Dutch Cardiovascular Alliance (DCVA) grant Double Dose 2021; and the Leducq Foundation grant number 20CVD01. Prof. Thum is supported by the EU (Grant Cardioregenix, GA 825670), the Deutsche Forschungsgemeinschaft DFG (TH903/20-2 and INST 95/15641). Conflict of interest: The UMCG, which employs Prof. de Boer, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. S.H. received personal fees for scientific advice from AstraZeneca, CSL Behring, Cellprothera, Bayer and Merck; and an unrestricted research grant from Pfizer. A.J.S.C. declares no conflicts related to this work. Outside of this work, in the last 3 years, he declares having received honoraria and/or lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Menarini, Novartis, Nutricia, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Gore, Impulse Dynamics and Respicardia. S.D. holds patents on microRNA therapeutics. T.E. and L.C. hold a patent on gene-therapy vectors for treating cardiomyopathy that was licensed to DiNAQOR AG, are members of the DiNAQOR Scientific Advisory Board, and have shares in DiNAQOR. The APHP, which employs Prof. Hulot, has received research grants from Bioserenity, Sanofi, Servier and Novo Nordisk. Outside of this work, J.S.H. has received speaker, advisory board or consultancy fees from Amgen, AstraZeneca, Bayer, Bioserenity, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis and Novo Nordisk. R.K. is an employee of AstraZeneca. C.K. holds a patent on AAV-based gene editing for Duchenne muscular dystrophy and has received advisor or speaker fees from AstraZeneca and AskBio. C.E.S. is a founder of Myokardia (a Bristol-Myers-Squibb Subsidiary); a consultant of Maze and BridgeBio; and is member of the Board of Directors at Merck. C.G.T. has received funding from Amgen and personal fees from Vivalyfe, outside of the submitted work, and is listed as an inventor on two heart failure patents. Prof. Seferovic declares consulting fees for Boehringer Ingelheim, Novartis, Vifor Pharma; and honoraria for lectures for Servier, AstraZeneca, Respicardia, Boehringer Ingelheim, and Novartis. T.T. has filed and licensed patents in the field of noncoding RNAs; he is founder and shareholder of Cardior Pharmaceuticals GmbH and is on the advisory board and/or received speaker fees from Novo Nordisk, Boehringer Ingelheim, Takeda, Amicus Therapeutics, Ksilink and Sanofi-Genzyme. Publisher Copyright: © 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Genetic cardiomyopathies are disorders of the cardiac muscle, most often explained by pathogenic mutations in genes encoding sarcomere, cytoskeleton, or ion channel proteins. Clinical phenotypes such as heart failure and arrhythmia are classically treated with generic drugs, but aetiology-specific and targeted treatments are lacking. As a result, cardiomyopathies still present a major burden to society, and affect many young and older patients. The Translational Committee of the Heart Failure Association (HFA) and the Working Group of Myocardial Function of the European Society of Cardiology (ESC) organized a workshop to discuss recent advances in molecular and physiological studies of various forms of cardiomyopathies. The study of cardiomyopathies has intensified after several new study setups became available, such as induced pluripotent stem cells, three-dimensional printing of cells, use of scaffolds and engineered heart tissue, with convincing human validation studies. Furthermore, our knowledge on the consequences of mutated proteins has deepened, with relevance for cellular homeostasis, protein quality control and toxicity, often specific to particular cardiomyopathies, with precise effects explaining the aberrations. This has opened up new avenues to treat cardiomyopathies, using contemporary techniques from the molecular toolbox, such as gene editing and repair using CRISPR-Cas9 techniques, antisense therapies, novel designer drugs, and RNA therapies. In this article, we discuss the connection between biology and diverse clinical presentation, as well as promising new medications and therapeutic avenues, which may be instrumental to come to precision medicine of genetic cardiomyopathies.
AB - Genetic cardiomyopathies are disorders of the cardiac muscle, most often explained by pathogenic mutations in genes encoding sarcomere, cytoskeleton, or ion channel proteins. Clinical phenotypes such as heart failure and arrhythmia are classically treated with generic drugs, but aetiology-specific and targeted treatments are lacking. As a result, cardiomyopathies still present a major burden to society, and affect many young and older patients. The Translational Committee of the Heart Failure Association (HFA) and the Working Group of Myocardial Function of the European Society of Cardiology (ESC) organized a workshop to discuss recent advances in molecular and physiological studies of various forms of cardiomyopathies. The study of cardiomyopathies has intensified after several new study setups became available, such as induced pluripotent stem cells, three-dimensional printing of cells, use of scaffolds and engineered heart tissue, with convincing human validation studies. Furthermore, our knowledge on the consequences of mutated proteins has deepened, with relevance for cellular homeostasis, protein quality control and toxicity, often specific to particular cardiomyopathies, with precise effects explaining the aberrations. This has opened up new avenues to treat cardiomyopathies, using contemporary techniques from the molecular toolbox, such as gene editing and repair using CRISPR-Cas9 techniques, antisense therapies, novel designer drugs, and RNA therapies. In this article, we discuss the connection between biology and diverse clinical presentation, as well as promising new medications and therapeutic avenues, which may be instrumental to come to precision medicine of genetic cardiomyopathies.
KW - Cardiomyopathy
KW - Dilated cardiomyopathy
KW - Disease mechanism
KW - Gene therapy
KW - Heart failure
KW - Hypertrophic cardiomyopathy
KW - Molecular biology
KW - Pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85122892844&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ejhf.2414
DO - https://doi.org/10.1002/ejhf.2414
M3 - Article
C2 - 34969177
SN - 1388-9842
VL - 24
SP - 406
EP - 420
JO - European journal of heart failure
JF - European journal of heart failure
IS - 3
ER -