Tamoxifen therapy in a murine model of myotubular myopathy

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 and James J. Dowling ()
Additional contact information
Nika Maani: Program for Genetics and Genome Biology, Hospital for Sick Children
Nesrin Sabha: Program for Genetics and Genome Biology, Hospital for Sick Children
Kamran Rezai: Program for Genetics and Genome Biology, Hospital for Sick Children
Arun Ramani: Program for Genetics and Genome Biology, 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
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

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07057-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07057-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07057-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().