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Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice

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Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice. / Mearini, Giulia; Stimpel, Doreen; Geertz, Birgit; Weinberger, Florian; Krämer, Elisabeth; Schlossarek, Saskia; Mourot-Filiatre, Julia; Stoehr, Andrea; Dutsch, Alexander; Wijnker, Paul J M; Braren, Ingke; Katus, Hugo A; Müller, Oliver J; Voit, Thomas; Eschenhagen, Thomas; Carrier, Lucie.

in: NAT COMMUN, Jahrgang 5, 01.01.2014, S. 5515.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Mearini, G, Stimpel, D, Geertz, B, Weinberger, F, Krämer, E, Schlossarek, S, Mourot-Filiatre, J, Stoehr, A, Dutsch, A, Wijnker, PJM, Braren, I, Katus, HA, Müller, OJ, Voit, T, Eschenhagen, T & Carrier, L 2014, 'Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice', NAT COMMUN, Jg. 5, S. 5515. https://doi.org/10.1038/ncomms6515

APA

Mearini, G., Stimpel, D., Geertz, B., Weinberger, F., Krämer, E., Schlossarek, S., Mourot-Filiatre, J., Stoehr, A., Dutsch, A., Wijnker, P. J. M., Braren, I., Katus, H. A., Müller, O. J., Voit, T., Eschenhagen, T., & Carrier, L. (2014). Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice. NAT COMMUN, 5, 5515. https://doi.org/10.1038/ncomms6515

Vancouver

Mearini G, Stimpel D, Geertz B, Weinberger F, Krämer E, Schlossarek S et al. Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice. NAT COMMUN. 2014 Jan 1;5:5515. https://doi.org/10.1038/ncomms6515

Bibtex

@article{c47c1bd6fe034b6a817a47228020949f,
title = "Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice",
abstract = "Homozygous or compound heterozygous frameshift mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C) cause neonatal hypertrophic cardiomyopathy (HCM), which rapidly evolves into systolic heart failure and death within the first year of life. Here we show successful long-term Mybpc3 gene therapy in homozygous Mybpc3-targeted knock-in (KI) mice, which genetically mimic these human neonatal cardiomyopathies. A single systemic administration of adeno-associated virus (AAV9)-Mybpc3 in 1-day-old KI mice prevents the development of cardiac hypertrophy and dysfunction for the observation period of 34 weeks and increases Mybpc3 messenger RNA (mRNA) and cMyBP-C protein levels in a dose-dependent manner. Importantly, Mybpc3 gene therapy unexpectedly also suppresses accumulation of mutant mRNAs. This study reports the first successful long-term gene therapy of HCM with correction of both haploinsufficiency and production of poison peptides. In the absence of alternative treatment options except heart transplantation, gene therapy could become a realistic treatment option for severe neonatal HCM.",
author = "Giulia Mearini and Doreen Stimpel and Birgit Geertz and Florian Weinberger and Elisabeth Kr{\"a}mer and Saskia Schlossarek and Julia Mourot-Filiatre and Andrea Stoehr and Alexander Dutsch and Wijnker, {Paul J M} and Ingke Braren and Katus, {Hugo A} and M{\"u}ller, {Oliver J} and Thomas Voit and Thomas Eschenhagen and Lucie Carrier",
year = "2014",
month = jan,
day = "1",
doi = "10.1038/ncomms6515",
language = "English",
volume = "5",
pages = "5515",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice

AU - Mearini, Giulia

AU - Stimpel, Doreen

AU - Geertz, Birgit

AU - Weinberger, Florian

AU - Krämer, Elisabeth

AU - Schlossarek, Saskia

AU - Mourot-Filiatre, Julia

AU - Stoehr, Andrea

AU - Dutsch, Alexander

AU - Wijnker, Paul J M

AU - Braren, Ingke

AU - Katus, Hugo A

AU - Müller, Oliver J

AU - Voit, Thomas

AU - Eschenhagen, Thomas

AU - Carrier, Lucie

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Homozygous or compound heterozygous frameshift mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C) cause neonatal hypertrophic cardiomyopathy (HCM), which rapidly evolves into systolic heart failure and death within the first year of life. Here we show successful long-term Mybpc3 gene therapy in homozygous Mybpc3-targeted knock-in (KI) mice, which genetically mimic these human neonatal cardiomyopathies. A single systemic administration of adeno-associated virus (AAV9)-Mybpc3 in 1-day-old KI mice prevents the development of cardiac hypertrophy and dysfunction for the observation period of 34 weeks and increases Mybpc3 messenger RNA (mRNA) and cMyBP-C protein levels in a dose-dependent manner. Importantly, Mybpc3 gene therapy unexpectedly also suppresses accumulation of mutant mRNAs. This study reports the first successful long-term gene therapy of HCM with correction of both haploinsufficiency and production of poison peptides. In the absence of alternative treatment options except heart transplantation, gene therapy could become a realistic treatment option for severe neonatal HCM.

AB - Homozygous or compound heterozygous frameshift mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C) cause neonatal hypertrophic cardiomyopathy (HCM), which rapidly evolves into systolic heart failure and death within the first year of life. Here we show successful long-term Mybpc3 gene therapy in homozygous Mybpc3-targeted knock-in (KI) mice, which genetically mimic these human neonatal cardiomyopathies. A single systemic administration of adeno-associated virus (AAV9)-Mybpc3 in 1-day-old KI mice prevents the development of cardiac hypertrophy and dysfunction for the observation period of 34 weeks and increases Mybpc3 messenger RNA (mRNA) and cMyBP-C protein levels in a dose-dependent manner. Importantly, Mybpc3 gene therapy unexpectedly also suppresses accumulation of mutant mRNAs. This study reports the first successful long-term gene therapy of HCM with correction of both haploinsufficiency and production of poison peptides. In the absence of alternative treatment options except heart transplantation, gene therapy could become a realistic treatment option for severe neonatal HCM.

U2 - 10.1038/ncomms6515

DO - 10.1038/ncomms6515

M3 - SCORING: Journal article

C2 - 25463264

VL - 5

SP - 5515

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -