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Brain Involvement iN Dystrophinopathies

Objective

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.

Call for proposal

H2020-SC1-2019-Two-Stage-RTD
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

UNIVERSITY COLLEGE LONDON
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 726 494,26

Participants (18)

CONSORZIO FUTURO IN RICERCA
Italy
EU contribution
€ 332 664
Address
Via G Saragat 1 Blocco B
44122 Ferrara
Activity type
Research Organisations
ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands
EU contribution
€ 1 020 495,54
Address
Albinusdreef 2
2333 ZA Leiden
Activity type
Higher or Secondary Education Establishments
REGION HOVEDSTADEN
Denmark
EU contribution
€ 284 066,28
Address
Kongens Vaenge 2
3400 Hillerod
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
EU contribution
€ 469 096,08
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne
Activity type
Higher or Secondary Education Establishments
NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY
Japan
EU contribution
€ 0
Address
4-1-1 Ogawa Higashi
187 8502 Kodaira Tokyo
Activity type
Other
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 498 179,65
Address
Rue Michel Ange 3
75794 Paris
Activity type
Other
UNIVERSITE DE VERSAILLES SAINT-QUENTIN-EN-YVELINES.
France
EU contribution
€ 500 201,24
Address
Avenue De Paris 55
78035 Versailles
Activity type
Higher or Secondary Education Establishments
STICHTING KEMPENHAEGHE
Netherlands
EU contribution
€ 303 219,75
Address
Sterkselseweg 65
5590 AB Heeze
Activity type
Other
UNIVERSITA CATTOLICA DEL SACRO CUORE
Italy
EU contribution
€ 182 766
Address
Largo Gemelli 1
20123 Milano
Activity type
Higher or Secondary Education Establishments
UNIVERSIDAD COMPLUTENSE DE MADRID
Spain
EU contribution
€ 178 408,50
Address
Avenida De Seneca 2
28040 Madrid
Activity type
Higher or Secondary Education Establishments
IMAGINE INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES FONDATION
France
EU contribution
€ 165 585
Address
24 Bd Du Montparnasse
75015 Paris 15
Activity type
Research Organisations
TRANSPHARMATION IRELAND LTD
Ireland
EU contribution
€ 272 445
Address
3Rd Floor Ulysses House Foley Street
D01 W2T2 Dublin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST
United Kingdom
EU contribution
€ 41 096,50
Address
Great Ormond Street
WC1N 3JH London
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
STICHTING UNITED PARENT PROJECTS MUSCULAR DYSTROPHY
Netherlands
EU contribution
€ 165 687,50
Address
Koninginnelaan 69
3905 GG Veenendaal
Activity type
Other
SYNTHENA AG
Switzerland
EU contribution
€ 100 000
Address
Freiestrasse 3
3012 Bern
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
PEPGEN LIMITED

Participation ended

United Kingdom
EU contribution
€ 16 037,51
Address
Bioescalitor Innovation Building O
OX37FZ Oxford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
STICHTING DUCHENNE DATA FOUNDATION
Netherlands
EU contribution
€ 156 373,44
Address
Warmoesdreef 10
4614 HC Bergen Op Zoom
Activity type
Other
THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Ireland
EU contribution
€ 253 508,75
Address
College Green
2 Dublin
Activity type
Higher or Secondary Education Establishments