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"Myasthenias, a group of immune mediated neurological diseases: from etiology to therapy." (FIGHT-MG)
Date du début: 1 déc. 2009, Date de fin: 31 mai 2014 PROJET  TERMINÉ 

"Myasthenia Gravis (MG) is a heterogeneous rare autoimmune neurological disease affecting the neuromuscular junction (NMJ). The molecular events causing and maintaining MG are still unknown and current treatments do not lead to remission and entail considerable side-effects stressing the need for improved therapies. We will address the: 1. Natural course of disease: determine factors associated with disease onset and/or affecting the course of disease and patients' quality of life in subgroups of MG patients including children, twins, females and elderly patients. 2. Etiology of MG: identify new genetic, epigenetic and environmental risk factors and investigate immunological key molecules associated with MG onset. 3. Pathogenic mechanisms at the NMJ: a) study molecular changes in the NMJ by proteomic, genetic, epigenetic and microRNA analyses in MG patients and experimental models; b) analyze morphological changes at the NMJ in mouse models expressing YFP nerves and mice transgenic for mini-agrin; c) evaluate the capacity of muscle cell satellites from MG patients to regenerate muscle and form new endplates in immunodeficient mice. 4. New diagnostic and monitoring assays: a) identify pathogenic and protective factors in MG sera; b) improve the sensitivity of current assays; c) Identify new biomarkers associated with different MG subgroups by proteomic and microRNA analyses; d) Identify patients' response to treatment and liability to side effects by pharmacogenomic analyses. 5. Novel therapies: a) study new cell-based therapies aimed at regulating the autoimmune response by regulatory T cells or mesenchymal stem cells in humanized mice; b) immunoadsorb pathogenic antibodies; c) test non-cell based immmunomodulatory therapies; d) target epigenetic regulators. This multidisciplinary project linking basic researchers with clinical neurologists, SMEs and several European patient associations should favor a translational approach for improved MG management"



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