Objective
Duchenne muscular dystrophy (DMD) is a progressive, lethal muscle degenerative condition arising from the absence of dystrophin in skeletal and cardiac muscles. 65% of DMD boys have out-of-frame deletions. Modulation of pre-mRNA splicing by exon skipping is the most promising molecular intervention in DMD. 2 Phase Ib and 2 Phase IIa clinical trials (MDEX Consortium in collaboration with Sarepta Therapeutics; a Dutch Consortium) demonstrated that delivery of antisense oligonucleotides (AOs) to mediate exon skipping of exon 51 were able to return specific DMD mutations in-frame (~13% of all mutations) leading to new dystrophin protein expression after intramuscular and systemic delivery. The Dutch study of repeated 2-O-methylated phosphorothioate (2OMe) AO administration suggested limited efficacy after 5 weeks of treatment. Our MDEX Consortium study using a morpholino (PMO) AO demonstrated a clear dose response, robust dystrophin restoration and reduction of muscle inflammation after 12 weeks at doses up to 20mg/Kg, with no drug related adverse events. This, and preclinical studies focused on level of protein expression, clearly indicate that PMO have a superior therapeutic index compared to 2OMe. New PMOs are needed to target other DMD mutations. We will develop a PMO to skip exon 53 and perform a clinical trial in DMD boys using a world leading pan-European consortium. This will allow us to advance this class of PMO therapy in DMD by i. assessing the safety and efficacy of targeting another exon; ii. exploring the use of non-invasive techniques to monitor dystrophin restoration. This new PMO will be administered over 12 weeks in 3 groups, each of 4 DMD boys, receiving between 4 to 30mg/kg or placebo. If well tolerated, all boys will be treated for another 24 weeks at a dose of 30mg/kg. Safety and dystrophin restoration in a muscle biopsy at the end of this period will be the study endpoints. MRI, MRS and serum miRNA will be used to monitor muscle pathology non-invasively.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology muscular dystrophies duchenne muscular dystrophy
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine pathology
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Programme(s)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-HEALTH-2012-INNOVATION-1
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
WC1E 6BT LONDON
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