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TAMYOCAL SIGNED

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

Total Cost €

0

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.

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

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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