DYSTROPHIC-ECM · Active role of skeletal muscle extracellular matrix in muscular dystrophies
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-07-01 → 2025-03-31
- EU contribution
- €295,062
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Active role of skeletal muscle extracellular matrix in muscular dystrophies
• What is the problem/issue being addressed? Muscular dystrophies are genetic diseases affecting 1:5000 males. Muscular dystrophies are characterized by progressive loss of function of muscle tissue that leads to premature death. Current treatments for muscular dystrophies, such as the use of corticosteroids, physical and respiratory therapy and cardiac management, act as palliative. Research into muscular dystrophies has previously focused on muscle cells. We propose to change perspective by analysing the muscle environment: the extracellular matrix (ECM). ECM is fundamental for muscle integrity and function. The discovery of one or more molecules of the ECM involved in the molecular mechanism of the pathology, will offer new therapeutic targets for the treatment of the disease. • Why is it important for society? The high cost for treatment and care and the poor quality of life for patients, mostly kids and young people, urge the society to invest in finding a cure. • What are the overall objectives? The objective of the project is to identify molecular alterations in the extracellular matrix (ECM) of skeletal muscle affected by muscular dystrophies and to investigate how these alterations affect the behaviour of muscle cells, directly contributing to the disease. We will take advantage of innovative strategies, techniques and technologies to identify molecular alterations in ECM. The discovery of alterations in dystrophic skeletal muscle ECM which actively impact the disease can contribute to identify new therapeutic targets for affected patients for whom an effective treatment does not exist.
Data: CORDIS, © European Union
Project objective
Most of the muscular dystrophies (MDs) are due to defects the trans-membrane protein complex called Dystro-GlycanComplex, which is a structural and functional bridge between myofiber contractile apparatus and extracellular matrix(ECM).MD research is focused upon the cellular mechanisms of the pathology and there is a lack of information about howECM molecules can affect MDs, although alteration in ECM composition is acknowledged since fibrosis is an important badoutcome in the patients.Our hypothesis is that alterations in dystrophic muscle ECM directly account for mechanisms whichnegatively affect skeletal muscle homeostasis.The goal of the project is to identify alterations in ECM compromised bymuscular dystrophy and to investigate their effects on cell behavior.Mdx mouse (model for Duchenne Muscular Dystrophy)and Sarcoglycan-β-null mouse (model for Limb Girdle Muscular Dystrophy 2E) will be used.To obtain the ECMs we will takeadvantage of decellularization approach that removes the cellular components while maintaining the molecular and structuralfeatures as closer as possible to the native ECM.In tissue engineering the use of ECM biomaterials demonstrated that ECMplays a fundamental, active role in tissue remodeling by growth factors release and ECM degradation productaction.Molecular alterations in the ECM composition will be investigated by proteomics that assures an accurate andexhaustive characterization.ECM will be used as 3D environment to study its functions in the behavior of primary cellsinvolved in the pathology: myogenic stem cells, endothelial cells, fibro-adipogenic precursors and macrophages.Discoveringhow alterations in dystrophic muscle ECM affect myogenesis, angiogenesis, fibrosis and inflammatory response will be ofparamount importance for a better understanding of MDs.Changing the focus of the research from the cells to the ECM, thisstudy will provide a new point of view and could contribute to identify new therapeutic targets.
Original text from CORDIS.
Participants
- UNIVERSITE LYON 1 CLAUDE BERNARD · Villeurbanne CedexCoordinatorFrance
Links
Data: CORDIS, © European Union