Objective
Duchenne muscular dystrophy (DMD) stems from loss of dystrophin in skeletal and cardiac muscles, which leads to loss of ambulation and cardio-respiratory failure. The most promising treatment that could be applicable to 83% of DMD patients is exon skipping, a technology where the EU is a world leader. Antisense oligonucleotide mediated exon skipping targets DMD pre-mRNA to induce skipping of specific exons and restore the open reading frame. This allows expression of shorter dystrophin proteins that lack domains encoded by the skipped exon(s). A crucial question is how to predict which short dystrophins will be stable and functional. This knowledge is fundamental to select DMD patients that would most benefit from this treatment and identify exons worth targeting via exon skipping.
The goal of this proposal is to develop a new use of exon skipping technology to rapidly generate mouse models to screen short dystrophins for in vivo stability and functionality in both skeletal and cardiac muscles. This is made possible by a new exon skipping chemistry developed in the UK with unparalleled skipping efficiency in vivo and capable of targeting the heart. I will use this technology to create mouse models for two short dystrophins generated in DMD patients undergoing exon 51 skipping in the current UK clinical trial. I will then biochemically assess their stability and functionality in limb, cardiac and respiratory muscles. Parallel histological studies will assess the presence of muscle pathology with a focus on heart and diaphragm that cannot be sampled in DMD patients. This project will serve as a trampoline for future studies to identify dystrophin exons that when skipped will produce functional proteins with clinical benefits. In addition, this research will generate new fundamental knowledge on dystrophin domains critical for muscle function and may help in the prognosis of DMD patients currently undergoing exon 51 skipping.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs
- medical and health sciences basic medicine neurology muscular dystrophies duchenne muscular dystrophy
- medical and health sciences basic medicine pathology
- medical and health sciences clinical medicine cardiology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
Funding Scheme
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.
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.
MSCA-IF-EF-RI - RI – Reintegration panel
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2014
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
WC1E 6BT LONDON
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.