Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy

Elinam Gayi, Laurence A. Neff, Xènia Massana Muñoz, Hesham M. Ismail, Marta Sierra, Thomas Mercier, Laurent A. Décosterd, Jocelyn Laporte, Belinda S. Cowling, Olivier M. Dorchies () and Leonardo Scapozza ()
Additional contact information
Elinam Gayi: University of Geneva
Laurence A. Neff: University of Geneva
Xènia Massana Muñoz: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
Hesham M. Ismail: University of Geneva
Marta Sierra: University of Geneva
Thomas Mercier: Lausanne University Hospital
Laurent A. Décosterd: Lausanne University Hospital
Jocelyn Laporte: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
Belinda S. Cowling: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
Olivier M. Dorchies: University of Geneva
Leonardo Scapozza: University of Geneva

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract X-linked myotubular myopathy (XLMTM, also known as XLCNM) is a severe congenital muscular disorder due to mutations in the myotubularin gene, MTM1. It is characterized by generalized hypotonia, leading to neonatal death of most patients. No specific treatment exists. Here, we show that tamoxifen, a well-known drug used against breast cancer, rescues the phenotype of Mtm1-deficient mice. Tamoxifen increases lifespan several-fold while improving overall motor function and preventing disease progression including lower limb paralysis. Tamoxifen corrects functional, histological and molecular hallmarks of XLMTM, with improved force output, myonuclei positioning, myofibrillar structure, triad number, and excitation-contraction coupling. Tamoxifen normalizes the expression level of the XLMTM disease modifiers DNM2 and PI3KC2B, likely contributing to the phenotypic rescue. Our findings demonstrate that tamoxifen is a promising candidate for clinical evaluation in XLMTM patients.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07058-4 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_s41467-018-07058-4

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

DOI: 10.1038/s41467-018-07058-4

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 ().