ArticleCell death & disease2016
Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in a patient-specific model of recessive catecholaminergic polymorphic ventricular tachycardia.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Advanced in vitro cardiac models for drug evaluation: integration of organoids, engineered tissues, and microphysiological systems.Microsystems & nanoengineering · 2026Review
- The emerging role of calsequestrin 2: from calcium sensor and modulator to arrhythmia driver.Journal of physiology and biochemistry · 2026Review
- The role of iPSC research for insight into inherited arrhythmia conditions.Heart rhythm · 2025Review
- Review
- Review
- Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024Review
- Article
- Catecholaminergic Polymorphic Ventricular Tachycardia and Gene Therapy: A Comprehensive Review of the Literature.Cureus · 2023Review
- Functional Characterisation of the RareInternational journal of molecular sciences · 2023Article
- Optical modulation of excitation-contraction coupling in human-induced pluripotent stem cell-derived cardiomyocytes.iScience · 2023Article
- Article
- Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.Nature communications · 2022Article
- The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.Biophysical reviews · 2022Review
- Cardiac calcium regulation in human induced pluripotent stem cell cardiomyocytes: Implications for disease modeling and maturation.Frontiers in cell and developmental biology · 2022Review
- An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation.Molecular medicine (Cambridge, Mass.) · 2021Article
- Pathogenesis of arrhythmogenic cardiomyopathy: role of inflammation.Basic research in cardiology · 2021Review
- Patient-specific induced pluripotent stem cells as "disease-in-a-dish" models for inherited cardiomyopathies and channelopathies - 15 years of research.World journal of stem cells · 2021Review
- The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes.Pflugers Archiv : European journal of physiology · 2021Review
- hiPSC-Derived Cardiac Tissue for Disease Modeling and Drug Discovery.International journal of molecular sciences · 2020Review
- Vagus nerve stimulation optimized cardiomyocyte phenotype, sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling.Cell death & disease · 2020Article
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14 authors.
Funding
Abstract
Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse model of the disease homozygous carrier of the R33Q mutation. In the present study, we investigated the efficacy of the virally mediated gene therapy in cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs) obtained from a patient carrying the homozygous CASQ2-G112+5X mutation. To this end, we infected cells with an Adeno-Associated Viral vector serotype 9 (AAV9) encoding the human CASQ2 gene (AAV9-hCASQ2). Administration of the human WT CASQ2 gene was capable and sufficient to restore the physiological expression of calsequestrin-2 protein and to rescue functional defects of the patient-specific iPSC-derived CMs. Indeed, after viral gene transfer, we observed a remarkable decrease in the percentage of delayed afterdepolarizations (DADs) developed by the diseased CMs upon adrenergic stimulation, the calcium transient amplitude was re-established and the density and duration of calcium sparks were normalized. We therefore demonstrate the efficacy of the AAV9-mediated gene replacement therapy for CPVT2 in a human cardiac-specific model system, supporting the view that the gene-therapy tested is curative in models with different human mutations of CPVT.
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