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Tamoxifen therapy in a murine model of myotubular myopathy

Author

Listed:
  • Nika Maani

    (Program for Genetics and Genome Biology, Hospital for Sick Children
    University of Toronto, Medical Science Building)

  • Nesrin Sabha

    (Program for Genetics and Genome Biology, Hospital for Sick Children
    University of Toronto, Medical Science Building
    University of Toronto)

  • Kamran Rezai

    (Program for Genetics and Genome Biology, Hospital for Sick Children
    University of Toronto, Medical Science Building)

  • Arun Ramani

    (Program for Genetics and Genome Biology, Hospital for Sick Children
    University of Toronto
    Centre for Computational Medicine, The Hospital for Sick Children)

  • Linda Groom

    (University of Rochester Medical Center School of Medicine and Dentistry)

  • Nadine Eltayeb

    (Program for Genetics and Genome Biology, Hospital for Sick Children)

  • Faranak Mavandadnejad

    (Program for Genetics and Genome Biology, Hospital for Sick Children)

  • Andrea Pang

    (Program for Genetics and Genome Biology, Hospital for Sick Children)

  • Giulia Russo

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP))

  • Michael Brudno

    (Program for Genetics and Genome Biology, Hospital for Sick Children
    University of Toronto
    Centre for Computational Medicine, The Hospital for Sick Children)

  • Volker Haucke

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP))

  • Robert T. Dirksen

    (University of Rochester Medical Center School of Medicine and Dentistry)

  • James J. Dowling

    (Program for Genetics and Genome Biology, Hospital for Sick Children
    University of Toronto, Medical Science Building
    University of Toronto)

Abstract

Myotubular myopathy (MTM) is a severe X-linked disease without existing therapies. Here, we show that tamoxifen ameliorates MTM-related histopathological and functional abnormalities in mice, and nearly doubles survival. The beneficial effects of tamoxifen are mediated primarily via estrogen receptor signaling, as demonstrated through in vitro studies and in vivo phenotypic rescue with estradiol. RNA sequencing and protein expression analyses revealed that rescue is mediated in part through post-transcriptional reduction of dynamin-2, a known MTM modifier. These findings demonstrate an unexpected ability of tamoxifen to improve the murine MTM phenotype, providing preclinical evidence to support clinical translation.

Suggested Citation

  • Nika Maani & Nesrin Sabha & Kamran Rezai & Arun Ramani & Linda Groom & Nadine Eltayeb & Faranak Mavandadnejad & Andrea Pang & Giulia Russo & Michael Brudno & Volker Haucke & Robert T. Dirksen & James , 2018. "Tamoxifen therapy in a murine model of myotubular myopathy," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07057-5
    DOI: 10.1038/s41467-018-07057-5
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    Cited by:

    1. Jean-Philippe Leduc-Gaudet & Anais Franco-Romero & Marina Cefis & Alaa Moamer & Felipe E. Broering & Giulia Milan & Roberta Sartori & Tomer Jordi Chaffer & Maude Dulac & Vincent Marcangeli & Dominique, 2023. "MYTHO is a novel regulator of skeletal muscle autophagy and integrity," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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