Myasthenia Gravis: etiology, pathophysiological & therapeutic approaches
Myasthenia gravis is an autoimmune diseases; diseases that affect more than 5% of the population. These are multifactorial diseases involving genetic predispositions, hormonal implication, dysfunctions of the immune system, and are triggered by unidentified factors. Myasthenia gravis is due to autoantibodies directed against components of the neuromuscular junction, mainly the acetylcholine receptor (AChR, 85% of cases) but sometimes also against the muscle-specific tyrosine kinase receptor (MuSK) or the LRP4 protein interacting with agrin. These autoantibodies reduce the efficiency of neuromuscular transmission and lead to abnormal muscle fatigability.
The thymus is most likely the site of initiation of myasthenia gravis with anti-AChR antibodies. Histological abnormalities of the thymus are very common: 50-60% of the patients present follicular hyperplasia with ectopic germinal centers, and 10-15% of the patient present a tumor of the thymus (Thymoma). Thymectomy is one of the treatments proposed to these patients.
The research projects developed by the team aim to understand the etiological and pathophysiological mechanisms involved in myasthenia gravis and to propose new therapeutic approaches. More specifically, our objectives are to:
- Elucidate the etiological mechanisms involved in autoimmunity by analyzing the impact of sex hormones and endocrine disruptors in central tolerance processes.
- Understand the cellular and molecular mechanisms at the origin of thymus inflammation and remodeling observed in patients.
- Study the immunoregulatory defects in myasthenia gravis patients by studying the functional phenotype of peripheral and thymic cells by mass cytometry (CyTOF).
- Develop new therapeutic approaches. In this context, we are studying the immunomodulatory and therapeutic potential of mesenchymal stem cells, and the potential of molecules interfering with inflammatory pathways.
- Search for circulating biomarkers to follow the evolution of the disease and the response to treatments.
| Name | Position | ORCID |
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- Rozen Le Panse, Louis Dubertret, Bernard Coulomb. p38 Mitogen-activated Protein Kinase Activation by Ultraviolet A Radiation in Human Dermal Fibroblasts¶. Photochemistry and Photobiology, 2003, 78 (2), pp.168. <a target="_blank" href="https://dx.doi.org/10.1562/0031-8655(2003)0782.0.co;2">⟨10.1562/0031-8655(2003)0782.0.co;2⟩. ⟨hal-03442095⟩
- Bruno Pitard, Hélène Pollard, Onnik Agbulut, Olivier Lambert, Jean-Thomas Vilquin, et al.. A Nonionic Amphiphile Agent Promotes Gene Delivery In Vivo to Skeletal and Cardiac Muscles. Human Gene Therapy, 2002, 13 (14), pp.1767-1775. ⟨10.1089/104303402760293592⟩. ⟨hal-03824393⟩
- Daniel Skuk, Jean Thomas Vilquin, Jacques Tremblay. Experimental and therapeutic approaches to muscular dystrophies. Current Opinion in Neurology, 2002, 15 (5), pp.563-569. ⟨10.1097/00019052-200210000-00007⟩. ⟨hal-03824399⟩
- Albert Hagège, Jean-Thomas Vilquin, Patrick Bruneval, Philippe Menasché. Regeneration of the myocardium: a new role in the treatment of ischemic heart disease?. Hypertension, 2001, 38 (6), pp.1413-1415. ⟨10.1161/hy1201.099618⟩. ⟨hal-03824403⟩
- Bruno Pouzet, Saïd Ghostine, Jean-Thomas Vilquin, Isabelle Garcin, Marcio Scorsin, et al.. Is Skeletal Myoblast Transplantation Clinically Relevant in the Era of Angiotensin-Converting Enzyme Inhibitors?. Circulation, 2001, 104 (suppl 1), pp.I-223-I-228. ⟨10.1161/hc37t1.094593⟩. ⟨hal-03824409⟩
- Jt Vilquin, Pf Kennel, M Paturneau-Jouas, P Chapdelaine, N Boissel, et al.. Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular dystrophies. Gene Therapy, 2001, 8 (14), pp.1097-1107. ⟨10.1038/sj.gt.3301484⟩. ⟨hal-03824098⟩
- Bruno Pouzet, Jean-Thomas Vilquin, Albert Hagège, Marcio Scorsin, Emmanuel Messas, et al.. Factors affecting functional outcome after autologous skeletal myoblast transplantation. Annals of Thoracic Surgery, 2001, 71 (3), pp.844-851. ⟨10.1016/s0003-4975(00)01785-9⟩. ⟨hal-03824418⟩
- Philippe Menasché, Albert Hagège, Marcio Scorsin, Bruno Pouzet, Michel Desnos, et al.. Myoblast transplantation for heart failure. The Lancet, 2001, 357 (9252), pp.279-280. ⟨10.1016/S0140-6736(00)03617-5⟩. ⟨hal-03824102⟩
- B. Pouzet, J.-T. Vilquin, A. Hagege, M. Scorsin, E. Messas, et al.. Intramyocardial Transplantation of Autologous Myoblasts : Can Tissue Processing Be Optimized?. Circulation, 2000, 102 (Supplement 3), pp.III-210-III-215. ⟨10.1161/01.cir.102.suppl_3.iii-210⟩. ⟨hal-03824428⟩
- B. Pouzet, J.-T. Vilquin, A. Hagege, M. Scorsin, E. Messas, et al.. Intramyocardial Transplantation of Autologous Myoblasts : Can Tissue Processing Be Optimized?. Circulation, 2000, 102 (Supplement 3), pp.III-210-III-215. ⟨10.1161/01.cir.102.suppl_3.iii-210⟩. ⟨hal-03824106⟩
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