ArticleNature cardiovascular research2023
Plakophilin 2 gene therapy prevents and rescues arrhythmogenic right ventricular cardiomyopathy in a mouse model harboring patient genetics.
Article in Nature cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Therapeutic upregulation of gene expression in inherited cardiomyopathies from current approaches to future directions.Nature cardiovascular research · 2026Review
- Alpha protein kinase 3 gene therapy restores heart function in mouse and human models of cardiomyopathy.Nature cardiovascular research · 2026Article
- TGF-β2 signaling promotes cardiac fibrosis in arrhythmogenic right ventricular cardiomyopathy mediated by DSC2 deficiency.Acta pharmacologica Sinica · 2026Article
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Prioritizing Discovery and Advancements in Arrhythmia Therapies: NIH/NHLBI Workshop.JACC. Clinical electrophysiology · 2026Review
- Gene Therapy for Cardiovascular and Cerebrovascular Disease: Mechanisms, Translational Barriers, and the Road Ahead.Biomedicines · 2026Review
- CCDC120 phase separation contributes to desmosomal integrity and cardiac function.Nature communications · 2026Article
- Connexin-43 Restoration Alleviates Desmosomal Arrhythmogenic Cardiomyopathy.Circulation. Heart failure · 2026Article
- Disease models and AAV therapies ofMolecular therapy. Advances · 2026Review
- Novel PKP2 compound heterozygous mutations causing neonatal early-onset arrhythmogenic cardiomyopathy: insights into the synergistic pathogenicity of biallelic inactivation.Functional & integrative genomics · 2026Article
- Cardiac troponin T promoters lead the way: optimizing cardiac specificity in AAV-mediated gene therapy.Gene therapy · 2026Article
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- What Should a Clinical Cardiologist Know About Cardiogenetics?Journal of the American Heart Association · 2025Review
- Maintenance of Energy Metabolism Is an Integral Part of Plakophilin-2 and Desmosome Functions.JACC. Basic to translational science · 2025Article
- Gene Therapy for Inherited Cardiac Arrhythmias.Journal of cardiovascular translational research · 2025Review
- Article
- Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- Arrhythmogenic Cardiomyopathy: Towards Genotype Based Diagnoses and Management.Journal of cardiovascular electrophysiology · 2025Review
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- AAV9-mediated gene supplementation therapy prevents and rescues arrhythmogenic cardiomyopathy in Pnpla2-mutated mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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13 authors.
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Abstract
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a fatal genetic heart disease characterized by cardiac arrhythmias, in which fibrofatty deposition leads to heart failure, with no effective treatments. Plakophilin 2 (PKP2) is the most frequently mutated gene in ARVC, and although altered RNA splicing has been implicated, there are no models to study its effect and therapeutics. Here, we generate a mouse model harboring a PKP2 mutation (IVS10-1G>C) affecting RNA splicing, recapitulating ARVC features and sudden death starting at 4 weeks. Administering AAV-PKP2 gene therapy (adeno-associated viral therapy to drive cardiac expression of PKP2) to neonatal mice restored PKP2 protein levels, completely preventing cardiac desmosomal and pathological deficits associated with ARVC, ensuring 100% survival of mice up to 6 months. Late-stage AAV-PKP2 administration rescued desmosomal protein deficits and reduced pathological deficits including improved cardiac function in adult mice, resulting in 100% survival up to 4 months. We suggest that AAV-PKP2 gene therapy holds promise for circumventing ARVC associated with PKP2 mutations, including splice site mutations.
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