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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.

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

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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