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TAMYOCAL SIGNED

Tamoxifen mediated protection on X-linked centronuclear myopathy: a mechanistic and pre-clinical study

Total Cost €

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EC-Contrib. €

0

Partnership

0

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 TAMYOCAL project word cloud

Explore the words cloud of the TAMYOCAL project. It provides you a very rough idea of what is the project "TAMYOCAL" about.

hosting    dramatic    model    leg    linked    estrogen    players    patients    receptor    treatments    everolimus    missing    treatment    elucidating    myopathies    unbalanced    balance    determined    extends    congenital    prevents    enhancement    modulating    diseases    rescue    drugs    tamoxifen    caused    tam    premature    symptoms    action    severe    phosphatases    skeletal       compounds    phosphatase    efficacy    muscle    partly    male    parallel    treated    instrumental    combined    multiple    centronuclear    restricting    mtorc1    functional    estrogenic    options    shown    phosphoinositide    creatine    myotubularin    igf    approved    lipid    vivo    rationale    births    families    complete    acts    modulator    clinical    function    autophagy    mechanism    group    atrophy    mouse    absence    mice    therapeutic    explained    survival    selective    signalling    mimics    death    exact    xlcnm    idea    events    steroids    rare    molecular    lifespan    first    protects    positively    myopathy    wild    pilot    rate   

Project "TAMYOCAL" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE DE GENEVE 

Organization address
address: RUE DU GENERAL DUFOUR 24
city: GENEVE
postcode: 1211
website: www.unige.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 175˙419 €
 EC max contribution 175˙419 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE DE GENEVE CH (GENEVE) coordinator 175˙419.00

Map

 Project objective

X-linked centronuclear myopathy (XLCNM) is a severe congenital myopathy caused by the absence of lipid phosphatase myotubularin. XLCNM affects 1/50.000 male births, there is no treatment and many cases lead to premature death. Thus, treatments are needed. Tamoxifen (TAM) is a selective estrogen receptor modulator that mimics estrogen signalling in skeletal muscle. Pilot study and previous results from the hosting group, have shown that TAM improve muscle symptoms and survival rate in XLCNM mouse model. Results strongly support the idea that TAM protects skeletal muscle via enhancement of estrogenic signalling positively modulating multiple pathways linked to muscle function. However, the exact mechanism(s) is not yet understood. This project aims at elucidating the mechanism(s) of action of TAM and evaluate further its efficacy in XLCNM mouse model. Two specific aims are proposed. First, to determine how TAM acts on pathways and key players involved in XLCNM. Estrogen signalling, phosphoinositide balance, autophagy and mTORC1 signalling will be determined in wild type and XLCNM mice treated and non-treated by TAM. Second, to investigate the pre-clinical efficacy of TAM combined with other compounds in XLCNM mice. TAM extends the lifespan of XLCNM mice according to the pilot study but it prevents only partly leg muscle atrophy, restricting complete functional rescue. Thus, TAM will be combined with other approved drugs that target muscle atrophy (everolimus, creatine, IGF-I and steroids). These parallel approaches will provide knowledge about not-yet explained events related to XLCNM and TAM effects, from molecular to in-vivo level, and instrumental information for other myopathies and rare diseases where lipid phosphatases are missing and phosphoinositide are unbalanced. This knowledge might provide the rationale for new therapeutic options for these dramatic conditions, being highly relevant to patients and families.

 Publications

year authors and title journal last update
List of publications.
2018 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, Leonardo Scapozza
Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07058-4
Nature Communications 9/1 2019-05-18

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