UMRS 582 was created in 2003 to contribute to the understanding of the molecular mechanisms involved in the rare pathologies of the striated muscle.

 

Directed by Dr Pascale Guicheney, DR1, UMRS 582 is composed of 7 teams conducting fundamental and clinical research into rare pathologies affecting the skeletal striated muscle and the cardiac muscle:

 

· congenital muscular dystrophies
· congenital myopathies
· ventricular arrhythmias
· laminopathies
· hypertrophic cardiomyopathies
· congenital myasthenic syndromes
· mitochondrial pathologies

 

The nosology of these pathologies is far from complete despite the identification of various genes in recent years. In UMRS 582 the teams are working in close collaboration on the following research themes:

 

 

These pathologies are clinically and genetically very heterogeneous. The identification of new genes rests on the definition of homogeneous entities themselves based on the determination of clinical, biological, morphological ultrastructural and immunocytochemical diagnostic criteria. Numerous French and foreign partners are contributing to this work, among whom clinicians and scientists of the Institute of Myology and the Pitié-Salpêtrière Hospital.

 

 

Since the identification of the genetic causes of certain diseases in the Unit,  pathophysiological studies have developed considerably, in particular opening the way for the study of lamins A/C, selenoprotein N, type VI collagen, dynamin 2, and mitofusins. For the projects concerning recently identified proteins such as mitofusins and selenoprotein N, our studies consist in determining their cellular functions.
For the projects concerning lamins, cardiac protein C, type VI collagen, dynamin 2 and synaptic proteins, we are developing cellular and animal models in order to demonstrate the pathophysiological consequences induced by mutations of the genes encoding these proteins. Our cellular models are varied – both cell lines, skin fibroblasts, cardiac and skeletal muscle cells, as well as nerve-muscle co-cultures. As for our animal models, they are obtained by knock-in or knock-out methods.

 

 

We are pursuing the development of therapies for diseases of the striated muscle. We are seeking to improve the efficacy of DNA transfer by non-viral vectors for gene therapy, to optimise myoblast transfer for cell therapy, and to test pharmacological approaches to prevent disease evolution.

 

UMRS 582 includes the following support team:

 

- Secretariat-Gestion: S. Sandal, Inserm; N Mahmoudi
- Technical management: A. Rouche, Inserm
- Photography: P. Bozin, Inserm
- Laundry: M. Benollol, Inserm; C. L'Hermitte Stead, Inserm
- Animal house: A. Salmon, Inserm