Gene therapy in cardiomyopathies - Review of the latest reports
DOI:
https://doi.org/10.12775/QS.2025.43.61280Keywords
cardiomyopathy, gene editing, antisense therapy, gene expression, gene replacement, ethical issuesAbstract
Introduction and purpose
Gene therapy appears to be a promising treatment for patients with cardiomyopathy and innovative therapeutic option. The aim of this review is to present the latest gene therapy technologies, innovations, research in the treatment of cardiomyopathy and analysis of the ethical issues associated with the use of modern therapies.
Material and methods
This review is based on recent articles from the years 2020-2025 found in databases such PubMed, Elsevier.
Results
Gene editing through CRISPR-Cas technology allows for the modification of genetic material by making changes at precise locations what is highly useful in gene therapy. Gene Expression Regulation (RNAi) involves preventing the production of proteins by silencing a faulty gene. Antisense therapy (ASO) uses antisense oligonucleotides to exclude a particular exon and causes the translation process to stop. Gene replacement involves introducing a healthy copy of a mutated gene into the genome along with an appropriate vector.
Conclusions
Individual technologies in the treatment of cardiomyopathy show potential for treating patients in the future. It is also important to remember the ethical issues when using solutions based on gene therapy. Clinical trials in the future are necessary to further search for solutions for patients with cardiomyopathy.
References
1. Arbelo E, Protonotarios A, Gimeno JR, et al. The new 2023 ESC guidelines for the management of cardiomyopathies: a guiding path for cardiologist decisions. Eur Heart J. 2023 Oct 1;44(37):3503-3626. PMID: 38867869; PMCID: PMC11167974. https://doi.org/10.1093/eurheartj/ehad194
2. Kyriakopoulou E, Monnikhof T, Van Rooij E. Gene editing innovations and their applications in cardiomyopathy research. Dis Model Mech. 2023 May 24;16(5):dmm050088. PMCID: PMC10233723; PMID: 37222281. https://doi.org/10.1242/dmm.050088
3. Cheng S, Han Y, Jiang L, et al. National, regional, and global cardiomyopathy burden from 1990 to 2019. Front Cardiovasc Med. 2022 Nov 30;9:1042448. PMCID: PMC9748073; PMID: 36531740. https://doi.org/10.3389/fcvm.2022.1042448
4. Ciarambino T, Menna G, Sansone G, et al. Cardiomyopathies: An Overview. Int J Mol Sci. 2021 Jul 19;22(14):7722. PMCID: PMC8303989; PMID: 34299342. https://doi.org/10.3390/ijms22147722
5. Venturiello D, Giorgio P G, Perulli F, et al. Unveiling the Future of Cardiac Care: A Review of Gene Therapy in Cardiomyopathies. Int J Mol Sci. 2024 Dec 6;25(23):13147. PMID: 39684857; PMCID: PMC11642060. https://doi.org/10.3390/ijms252313147
6. Lopes LR, Ho CY , Elliott PM. Genetics of hypertrophic cardiomyopathy: established and emerging implications for clinical practice. Eur Heart J. 2024 Jul 10;45(30):2727–2734. PMCID: PMC11313585; PMID: 38984491. https://doi.org/10.1093/eurheartj/ehae421
7. Biddinger KJ, Jurgens SJ, Maamari D, et al. Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank. JAMA Cardiol. 2022 May 18;7(7):715-722. PMID: 35583889; PMCID: PMC9118016. https://doi.org/10.1001/jamacardio.2022.1061
8. Ditaranto R, Caponetti A G, Ferrara V, et al. Pediatric Restrictive Cardiomyopathies. Front Pediatr. 2022 Jan 25;9:745365. PMCID: PMC8822222; PMID: 35145940. https://doi.org/10.3389/fped.2021.745365
9. Szczygieł JA, Michałek P, Truszkowska G, et al. Clinical features, etiology, and survival in patients with restrictive cardiomyopathy: A single-center experience. Kardiol Pol. 2023 Nov 8;81(12):1227-1236. PMID: 37937352. https://doi.org/10.33963/v.kp.97879
10. Aquaro GD, De Luca A, Cappelletto C, et al. Prognostic Value of Magnetic Resonance Phenotype in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy. J Am Coll Cardiol. 2020 Jun 9;75(22): 2753-2765. https://doi.org/10.1016/j.jacc.2020.04.023
11. Wang Y, Jia H , Song J. Accurate Classification of Non-ischemic Cardiomyopathy. Curr Cardiol Rep. 2023 Sep 15;25(10):1299–1317. PMCID: PMC10651539; PMID: 37721634. https://doi.org/10.1007/s11886-023-01944-0
12. Kurakula H, Vaishnavi S, Sharif MY, et al. Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases. ACS Omega. 2023 Jun 1;8(23):20234–20250. PMCID: PMC10268023; PMID: 37323391. https://doi.org/10.1021/acsomega.3c01703
13. Liao H, Wu J , VanDusen NJ, et al. CRISPR-Cas9-mediated homology-directed repair for precise gene editing. Mol Ther Nucleic Acids. 2024 Sep 26;35(4):102344. PMCID: PMC11531618; PMID: 39494147. https://doi.org/10.1016/j.omtn.2024.102344
14. Dai Y, Amenov A, Ignatyeva N, et al. Troponin destabilization impairs sarcomere-cytoskeleton interactions in iPSC-derived cardiomyocytes from dilated cardiomyopathy patients. Sci Rep. 2020 Jan 14;10(1):209. PMID: 31937807; PMCID: PMC6959358. https://doi.org/10.1038/s41598-019-56597-3
15. Patel AG, Li P, Badrish N, et al. Transthyretin Cardiac Amyloidosis: Current and Emerging Therapies. Curr Cardiol Rep. 2025 Jan 22;27(1):33. PMCID: PMC11754378; PMID: 39841315. https://doi.org/10.1007/s11886-024-02172-w
16. Biagini E, Longhi S. More players in the treatment of transthyretin amyloidosis? The HELIOS-B study. Eur Heart J Suppl. 2025 Apr 16;27(Suppl 3):iii19–iii21. PMCID: PMC12001764; PMID: 40248307. https://doi.org/10.1093/eurheartjsupp/suaf009
17. Jankauskas SS, Varzideh F, Kansakar U, et al. Targeting miR-199a reduces fibrosis in hypertrophic cardiomyopathy. J Mol Cell Cardiol Plus. 2023 Dec 9;7:100057. PMCID: PMC11708307; PMID: 39802443. https://doi.org/10.1016/j.jmccpl.2023.100057
18. Chiti E, Di Paolo M, Turillazzi E, et al. MicroRNAs in Hypertrophic, Arrhythmogenic and Dilated Cardiomyopathy. Diagnostics (Basel). 2021 Sep 19;11(9):1720. PMCID: PMC8469137; PMID: 34574061. https://doi.org/10.3390/diagnostics11091720
19. Michaels WE, Pena-Rasgado C, Kotaria R, et al. Open reading frame correction using splice-switching antisense oligonucleotides for the treatment of cystic fibrosis. Proc Natl Acad Sci U S A. 2022 Jan 18;119(3):e2114886119. PMID: 35017302; PMCID: PMC8784102. https://doi.org/10.1073/pnas.2114886119
20. Shiba N, Yang X, Sato M, et al. Efficacy of exon-skipping therapy for DMD cardiomyopathy with mutations in actin binding domain 1. Mol Ther Nucleic Acids. 2023 Oct 19:34:102060. PMID: 38028197; PMCID: PMC10654596. https://doi.org/10.1016/j.omtn.2023.102060
21. Rodriguez-Polo I, Behr R. Exploring the Potential of Symmetric Exon Deletion to Treat Non-Ischemic Dilated Cardiomyopathy by Removing Frameshift Mutations in TTN. Genes (Basel). 2022 Jun 19;13(6):1093. PMID: 35741855; PMCID: PMC9222585. https://doi.org/10.3390/genes13061093
22. Beverborg NG, Später D, Knöll R, et al. Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy. Nat Commun. 2021 Aug 30;12:5180. PMCID: PMC8405807; PMID: 34462437. https://doi.org/10.1038/s41467-021-25439-0
23. Greer-Short A, Greenwood A, Leon EC , et al. AAV9-mediated MYBPC3 gene therapy with optimized expression cassette enhances cardiac function and survival in MYBPC3 cardiomyopathy models. Nat Commun. 2025 Mar 4;16:2196. PMCID: PMC11880196; PMID: 40038304. https://doi.org/10.1038/s41467-025-57481-7
24. Zhang H, Zhan O, Huang B, et al. AAV-mediated gene therapy: Advancing cardiovascular disease treatment. Front Cardiovasc Med. 2022 Aug 19:9:952755. PMID: 36061546; PMCID: PMC9437345. https://doi.org/10.3389/fcvm.2022.952755
25. Maurer MS, Kale P., Fontana M, et al. Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. N Engl J Med. 2023 Oct 26;389(17):1553-1565. PMID: 37888916; PMC: PMC10757426. https://doi.org/10.1056/NEJMoa2300757
26. Hong KN, Eshraghian EA, Arad M, et al. International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Oct 17;82(16):1628-1647. PMID: 37821174. https://doi.org/10.1016/j.jacc.2023.08.014
27. Umer M, Kalra DK. Treatment of Fabry Disease: Established and Emerging Therapies. Pharmaceuticals (Basel). 2023 Feb 20;16(2):320. PMCID: PMC9967779; PMID: 37259462. https://doi.org/10.3390/ph16020320
28. Eggers M , Vannoy CH, Huang J, et al. Muscle‐directed gene therapy corrects Pompe disease and uncovers species‐specific GAA immunogenicity. EMBO Mol Med. 2021 Dec 1;14(1):e13968. PMCID: PMC8749482; PMID: 34850579. https://doi.org/10.15252/emmm.202113968
29. Munoz-Zuluaga C, Gertz M, Yost-Bido M, et al. Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia. Hum Gene Ther. 2023 Jul 17;34(13-14):605–615. PMCID: PMC10354731; PMID: 37166361. https://doi.org/10.1089/hum.2023.020
30. Nishiyama T, Zhang Y, Cui M, et al. Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Sci Transl Med. 2022 Nov 23;14(672):eade1633. PMCID: PMC10088465; PMID: 36417486. https://doi.org/10.1126/scitranslmed.ade1633
31. Mendell JR, Sahenk z, Lehman KJ, et al. Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial. Muscle Nerve. 2024 Jan;69(1):93-98. Epub 2023 Aug 14. PMID: 37577753. https://doi.org/ 10.1002/mus.27955
32. Deng J, Zhang J, Shi K, et al. Drug development progress in duchenne muscular dystrophy. Front Pharmacol. 2022 Jul 22;13:950651. PMCID: PMC9353054; PMID: 35935842. https://doi.org/10.3389/fphar.2022.950651
33. Van Opbergen CJM, Narayanan B, Sacramento CB, et al. AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans. Circ Genom Precis Med. 2024 Feb;17(1):e004305. Epub 2024 Jan 30. PMID: 38288614; PMCID: PMC10923105. https://doi.org/10.1161/CIRCGEN.123.004305
34. Ayanoğlu FB, Elçin AE, Elçin YM. Bioethical issues in genome editing by CRISPR-Cas9 technology. Turk J Biol. 2020 Apr 2;44(2):110–120. PMCID: PMC7129066; PMID: 32256147. https://doi.org/10.3906/biy-1912-52
35. Markusic DM, Martino AT, Porada CD, et al. Immunology of Gene and Cell Therapy. Mol Ther. 2020 Feb 4;28(3):691–692. Epub 2020 Feb 4. PMCID: PMC7054825; PMID: 32023479. https://doi.org/10.1016/j.ymthe.2020.01.024
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Magdalena Strzelczyk, Gabriela Pabis, Joanna Wziątek , Paula Bętkowska , Iwona Koziołek , Piotr Kowalik , Patrycja Fatyga , Wiktoria Fatyga , Daria Krzyżanowska , Kinga Dowierciał
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 8
Number of citations: 0
