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Opendata, web and dolomites

TAMYOCAL SIGNED

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

Total Cost €

EC-Contrib. €

Partnership

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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.

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

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 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.	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

List of publications.
year	authors and title	journal	last update
2018	Elinam Gayi, Laurence A. Neff, XÃ¨nia Massana MuÃ±oz, Hesham M. Ismail, Marta Sierra, Thomas Mercier, Laurent A. DÃ©costerd, 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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