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
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesclinical medicinepsychiatryobsessive-compulsive disorder
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineneurologymuscular dystrophiesduchenne muscular dystrophy
- natural sciencesbiological sciencesgeneticsmutation
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
WC1E 6BT London
United Kingdom
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Participants (20)
44122 Ferrara
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
44121 Ferrara
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2333 ZA Leiden
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3400 Hillerod
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NE1 7RU Newcastle Upon Tyne
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187 8502 Kodaira Tokyo
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75794 Paris
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78035 Versailles
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
75654 Paris
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5590 AB Heeze
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20123 Milano
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28040 Madrid
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75015 Paris 15
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D01 W2T2 Dublin
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WC1N 3JH London
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3905 GG Veenendaal
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3012 Bern
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Participation ended
OX37FZ Oxford
4614 HC Bergen Op Zoom
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D02 CX56 Dublin 2
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