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Brain Involvement iN Dystrophinopathies

Objectif

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in childhood, with more than 25,000 patients in Europe. It is due to mutations in the DMD gene that preclude the production of the protein dystrophin. In addition to the progressive muscle weakness, 50% of affected individuals have debilitating central nervous system (CNS) co-morbidities, including intellectual disability, neurodevelopmental problems encompassing autism, Attention Deficit Hyperactivity Disorder and Obsessive Compulsive Disorder. These co-morbidities are due to the deficiency of multiple dystrophin isoforms in brain whose expression is differentially affected by the site of the DMD mutation. They represent a major obstacle for patients to live a fully independent life. Current therapies do not address these co-morbidities. The postnatal restoration of one dystrophin isoform using genetic therapies in the DMD mouse model improves the neurobehavioral phenotype. This raises the exciting possibility that some of the CNS co-morbidities could improve with genetic therapies in patients. We need to address several knowledge gaps before considering clinical applications of these therapies: i. dystrophin isoforms localisation in the CNS; ii. which of the neurobehavioural features of the dystrophic mice improve after dystrophin restoration, and circuitries involved; iii. deep phenotype patients to define robust outcome measures. This project developed in partnership with advocacy groups, meets gender criteria and offers for the first time insight into how dystrophins’ affect CNS function, and on the reversibility of the DMD CNS co-morbidities, providing essential information to the field of neurodevelopmental disorders, and for other syndromes arising from dystrophin associated proteins. Our efforts to develop novel therapies that can cross the blood brain barrier could be transformative for the field of neurodegeneration and neurodevelopmental disorders.

Appel à propositions

H2020-SC1-2019-Two-Stage-RTD
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Coordinateur

UNIVERSITY COLLEGE LONDON
Adresse
Gower Street
WC1E 6BT London
United Kingdom
Type d’activité
Higher or Secondary Education Establishments
Contribution de l’UE
€ 1 726 494,26

Participants (18)

CONSORZIO FUTURO IN RICERCA
Italie
Contribution de l’UE
€ 332 664
Adresse
Via G Saragat 1 Blocco B
44122 Ferrara
Type d’activité
Research Organisations
ACADEMISCH ZIEKENHUIS LEIDEN - LEIDS UNIVERSITAIR MEDISCH CENTRUM
Pays-Bas
Contribution de l’UE
€ 1 020 495,54
Adresse
Albinusdreef 2
2333 ZA Leiden
Type d’activité
Higher or Secondary Education Establishments
REGION HOVEDSTADEN
Danemark
Contribution de l’UE
€ 284 066,28
Adresse
Kongens Vaenge 2
3400 Hillerod
Type d’activité
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
Contribution de l’UE
€ 469 096,08
Adresse
Kensington Terrace 6
NE1 7RU Newcastle Upon Tyne
Type d’activité
Higher or Secondary Education Establishments
NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY
Japon
Contribution de l’UE
€ 0
Adresse
4-1-1 Ogawa Higashi
187 8502 Kodaira Tokyo
Type d’activité
Other
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
Contribution de l’UE
€ 498 179,65
Adresse
Rue Michel Ange 3
75794 Paris
Type d’activité
Research Organisations
UNIVERSITE DE VERSAILLES SAINT-QUENTIN-EN-YVELINES.
France
Contribution de l’UE
€ 500 201,24
Adresse
Avenue De Paris 55
78035 Versailles
Type d’activité
Higher or Secondary Education Establishments
STICHTING KEMPENHAEGHE
Pays-Bas
Contribution de l’UE
€ 303 219,75
Adresse
Sterkselseweg 65
5590 AB Heeze
Type d’activité
Other
UNIVERSITA CATTOLICA DEL SACRO CUORE
Italie
Contribution de l’UE
€ 182 766
Adresse
Largo Agostino Gemelli 1
20123 Milano
Type d’activité
Higher or Secondary Education Establishments
UNIVERSIDAD COMPLUTENSE DE MADRID
Espagne
Contribution de l’UE
€ 178 408,50
Adresse
Avenida Seneca 2 Edificio Seneca
28040 Madrid
Type d’activité
Higher or Secondary Education Establishments
IMAGINE INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES FONDATION
France
Contribution de l’UE
€ 165 585
Adresse
24 Bd Du Montparnasse
75015 Paris 15
Type d’activité
Research Organisations
TRANSPHARMATION IRELAND LTD
Irlande
Contribution de l’UE
€ 272 445
Adresse
3Rd Floor Ulysses House Foley Street
D01 W2T2 Dublin
Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Great Ormond Street Hospital for Children NHS Trust
United Kingdom
Contribution de l’UE
€ 41 096,50
Adresse
Great Omond Street
WC1N 3JH London
Type d’activité
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
STICHTING UNITED PARENT PROJECTS MUSCULAR DYSTROPHY
Pays-Bas
Contribution de l’UE
€ 165 687,50
Adresse
Koninginnelaan 69
3905 GG Veenendaal
Type d’activité
Other
SYNTHENA AG
Suisse
Contribution de l’UE
€ 100 000
Adresse
Freiestrasse 3
3012 Bern
Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
PEPGEN LIMITED

Participation terminée

United Kingdom
Contribution de l’UE
€ 16 037,51
Adresse
Bioescalitor Innovation Building O
OX37FZ Oxford
Type d’activité
Private for-profit entities (excluding Higher or Secondary Education Establishments)
STICHTING DUCHENNE DATA FOUNDATION
Pays-Bas
Contribution de l’UE
€ 156 373,44
Adresse
Warmoesdreef 10
4614 HC Bergen Op Zoom
Type d’activité
Other
THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Irlande
Contribution de l’UE
€ 253 508,75
Adresse
College Green
2 Dublin
Type d’activité
Higher or Secondary Education Establishments