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.
Fields of science
- medical and health sciencesbasic medicineneurologymuscular dystrophyduchenne muscular dystrophy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgenetics and hereditymutation
- medical and health sciencesclinical medicinepsychiatryobsessive-compulsive disorder
- natural sciencesbiological sciencesneurobiology
Programme(s)
Call for proposal
H2020-SC1-2019-Two-Stage-RTD
See other projects for this call
Funding Scheme
RIA - Research and Innovation actionCoordinator
WC1E 6BT London
United Kingdom
Participants (18)
44122 Ferrara
2333 ZA Leiden
3400 Hillerod
NE1 7RU Newcastle Upon Tyne
187 8502 Kodaira Tokyo
75794 Paris
78035 Versailles
5590 AB Heeze
20123 Milano
28040 Madrid
75015 Paris 15
D01 W2T2 Dublin
WC1N 3JH London
3905 GG Veenendaal
3012 Bern
Participation ended
OX37FZ Oxford
4614 HC Bergen Op Zoom
2 Dublin