Team 1- Genetics, Pathophysiology & Therapeutic approaches of muscle diseases

equipe1

Team leader : Gisèle Bonne

Neuromuscular disorders (NMD) are highly heterogeneous diseases, both clinically and genetically, for which no treatment is available yet. In order to conceive and develop therapeutic approaches for these disorders, a comprehensive knowledge of their natural history (clinical, histopathology, genetics, and biochemical defects) and a refined comprehension of the underlying pathophysiological mechanisms are essential.

Our research is focused on two groups of “contractile” myopathies: collagen type VI-related muscle disorders (Allamand et al. 2011, Sk Muscle) and Emery-Dreifuss muscular dystrophies (EDMD) & other striated muscle laminopathies (SML) (Bertrand et al. 2011 Biochem Soc Trans; Azibani et al. 2014 Semin Cell Dev Biol.).

Our activities have led to the identification of genetic defects, the development of tools (cellular and animal models) and the exploration of pathomechanistic hypotheses that refine our understanding of the molecular bases and the discovery of therapeutic targets for these disorders. Many questions concerning these diseases remain unanswered: absence of molecular diagnosis for a subset of patients, implicated protein function and pathophysiological mechanisms. Several common points (contractile dysfunction, mechano-biology, autophagy, fibrosis) have been and are still addressed transversally through pooling of our expertise (nucleus, extracellular matrix, contractile proteins, cell trafficking).

Our main objectives for the coming years are as follows:

  1. Defining the genetic and clinical spectrum and the natural history of collagen type VI-related muscle disorders & ECM-related disorders and of EDMD & other striated muscle laminopathies,
  2. Investigating the pathophysiological mechanisms of the gene mutations,
  3. Identifying and testing therapeutic avenues for these disorders.

These objectives are carried out on biological material from patients (DNA, RNA, cultured cells and biopsies) as well as from animal models (mouse, zebrafish) we developed for each of the NMDs of interest.

Team members

EDMD & Striated muscle
Laminopathies
G Bonne, DR1 Inserm
 Collagen type VI-related
muscle disorders

V Allamand, DR2 Inserm
Pathophysiology and mechanobiology
of muscular disorders
C Coirault, DR2 Inserm
A Bertrand, CR AIM
A Muchir, CR1 Inserm
N Vignier, CR, AIM
I Nelson, IR AIM
A Brull Cañagueral, Post-doc (CDD)
B Morales Rodriguez, Doctoral student
D. Cardoso, Master Student
C Gartioux, TR, AIM
M Saunier, Doctoral student
N Essawi, Doctoral student

 

Transversal Activities, G Bonne, DR1 Inserm
Clinical expertise

D Duboc, PU-PH (5%)
F Leturcq, PH, AP (10%)
C Metay, PH, AP (10 %)
T Stojkovic, PH, AP (10%)
K Wahbi, MCU-PH, AP (10%)

Data bases

R Ben Yaou, CR, AIM (30%)
K Chikhaoui, ARC, AIM (30%)

Histopathology platform

NB Romero, PH, AP (10%)
M Beuvin, IE, AIM

 

Contacts

Gisèle Bonne  (g.bonne@institut-myologie.org)
Valérie Allamand (v.allamand@institut-myologie.org)
Catherine Coirault (c.coirault@institut-myolgogie.org)
Anne Bertrand (a.bertrand@institut-myologie.org)
Antoine Muchir (a.muchir@institut-myologie.org)
Nicolas Vignier (n.vignier@institut-myologie.org)