Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus
Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus
Our research interests focus on two groups of neuromuscular disorders (NMD): myopathies due to abnormalities of the myomatrix and of the nucleus. The long-term objective of our work is to propose relevant therapeutic options based on our knowledge of the genetic basis and of the underlying pathomechanisms at play in these rare diseases.
Research Project: Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus
Our team focuses on 2 groups of neuromuscular disorders: myopathies due to the defective myomatrix (collagen VI and other components of the extracellular matrix) and to defects of the myonucleus (Emery-Dreifuss muscular dystrophy and other striated muscle laminopathies due to mutations in the laminA/C gene or genes encoding components of nuclear membrane). These myopathies share some clinical features, notably prominent contractures, and constitute differential diagnosis[in1] .
These disorders are highly heterogeneous, clinically and genetically, and to date no treatment is available. Our previous work led us to identify the involvement of various genetic alterations and to develop tools (cellular and animal models) that are crucial for deciphering pathomechanisms, understanding the molecular defects and unveiling therapeutic targets.
We are still facing several challenges and bottlenecks: 1) a number of patients are still awaiting molecular diagnosis; 2) relevant biomarkers are scarce; 3) functions of the involved proteins and underlying pathomechanisms are still poorly understood … We previously have and continue to tackle several transverse processes (e.g. contractile dysfunction, defective mechanosensing, fibrosis …) using our specific expertise (nuclear envelop, nucleoplasm, extracellular matrix…).
Current research axes:
- Definition of genetic and clinical spectrum and delineation of natural history of these NMDs,
- Development of new tools to validate genetic variants identified through NGS (next generation sequencing),
- Deciphering pathomechanisms that affect skeletal and/or cardiac muscle, with the overall goal of identifying and assessing therapeutic options for these disorders.
Our work is carried out on biological material derived from patients (DNA, RNA cultured cells, or muscle biopsies), and on animal models developed in the team (mouse, zebrafish).
Noyau-MEC ©Astrid Brull
Contact:
| Name | Position | ORCID |
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- Gisèle Bonne, Martin Krahn. Concept de gènes actionnables et application dans le domaine neuromusculaire.. 25èmes Journées Neuromusculaires de Marseille, Sep 2023, Marseille, France. ⟨hal-04189737⟩
- Gisèle Bonne. Insights in the pathophysiological mechanisms of striated muscle Laminopathies. Ottawa NMD 2023 Conference, Sep 2023, Ottawa, Canada. ⟨hal-04189748⟩
- Louise Benarroch, Julia Madsen-Østerbye, Mohamed Abdelhalim, Kamel Mamchaoui, Jessica Ohana, et al.. Cellular and Genomic Features of Muscle Differentiation from Isogenic Fibroblasts and Myoblasts. Cells, 2023, 12 (15), pp.1995. ⟨10.3390/cells12151995⟩. ⟨hal-04187751⟩
- Gisèle Bonne. How to solve rare diseases: systematic pan-European data sharing and collaborative analysis: the Solve-RD project. 15th Congress of the European Paedriatric Neurology Society, European Paedriatric Neurology Society, Jun 2023, Prague, Czech Republic. ⟨hal-04189585⟩
- Gisèle Bonne. Insights in the pathophysiological mechanisms of striated muscle Laminopathies. European Meeting on Intermediate Filaments, Elly Hol, Jun 2023, Noorwijkerhout, Netherlands. ⟨hal-04189581⟩
- Gisèle Bonne. Le Treatabolome : une base de donnée des traitements existant pour les maladies rares à l’échelle du gène/variant. Webinaire de la Filière en Santé Filnemus, May 2023, Paris, France. ⟨hal-04189577⟩
- Anne T Bertrand, Mariko Okubo, Astrid Brull, Maud Beuvin, Nathalie Mougenot, et al.. Challenges in gene therapy for striated muscle laminopathy. 4th International Meeting on Laminopathies, May 2023, Madrid, Spain. ⟨10.3233/JND-239001⟩. ⟨hal-04170075⟩
- Valérie Decostre, Cathy Chikhaoui, Corinne Vigouroux, Susana Quijano-Roy, Karim Wahbi, et al.. Quantification of skeletal muscle strength in laminopathies. 4th International Meeting on Laminopathies, May 2023, Madrid, Spain. ⟨10.3233/JND-239001⟩. ⟨hal-04189561⟩
- Marine Leconte, Anne Bertrand, Zoheir Guesmia, Gisèle Bonne, Gisèle Bonne. DNA damage repair in LMNA-related congenital muscular dystrophy. 4th International Meeting on Laminopathies, May 2023, Madrid, Spain. ⟨10.3233/JND-239001⟩. ⟨hal-04189722⟩
- Rocio Garcia-Uzquiano, Marta Gomez-García de La Banda, Laure Le Goff, Veronique Manel, Ivana Dabaj, et al.. Steroid treatment may change natural history in congenital laminopathies. 4th International Meeting on Laminopathies, May 2023, Madrid, Spain. ⟨10.3233/JND-239001⟩. ⟨hal-04189730⟩
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Our last work on the OJRD
A guide to writing systematic reviews of rare disease treatments to generate FAIRcompliant datasets: building a Treatabolome