Heart failure & cardiomyopathies
Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2–Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors' conclusion
Our study reveals novel mechanisms of ARVC caused by DSC2 loss of function, supported by human and mouse data. Loss of Myl7 contributes to reduced cardiac contractility in ARVC and dilated cardiomyopathy with right ventricular systolic dysfunction. Dsc2 mRNA treatment demonstrated significant therapeutic potential in ARVC and transverse aortic constriction models
Study context
- Population
- Chinese family with autosomal recessive arrhythmogenic right ventricular cardiomyopathy (ARVC) (novel DSC2 variant); Dsc2 knock-in and knock-out mice; transverse aortic constriction mice
- Comparison
- Dsc2 mRNA treatment vs no treatment in Dsc2-deficient mice
Methodological detailshuman genetic and mouse model study
- Human genetic and mouse model study
Main finding
As reported in the abstract
- Dsc2-deficient mice exhibited RV dilation and dysfunction, mimicking human disease
- Myl7 the most downregulated gene in RV of Dsc2-deficient mice; restoration by adeno-associated virus 9 rescued heart function
- Dsc2 mRNA delivery, with or without lipid nanoparticle encapsulation, normalized heart size and function in Dsc2-deficient mice
- Single dose of mRNA gave therapeutic effects lasting 2 to 3 months before declining
Further findings
- Reduced DSC2 and MLC2a expression in patients with noninherited dilated cardiomyopathy and in mice with transverse aortic constriction
Original publication
Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2–Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. Published 11 April 2025. doi:10.
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