MYASTAID - Development of models to improve management of Myasthenia Gravis: From basic knowledge to clinical application (FP6-LIFESCIHEALTH) (2006-10-01 - 2009-09-30) (»add to infobox)

Sonia BERRIH-AKNIN, Socrates TZARTOS, Marc DE BAETS, Tsvee LAPIDOT, Orly EIZENBERG, Eugene BOSMANS, Paul PARREN, Nicolas PASQUAL, Orgad LAUB, Michael ROBERTS

UNIVERSITE PARIS-SUD (FR104 - Essonne) (France), HELLENIC PASTEUR INSTITUTE (GR300 - Attiki) (Greece), UNIVERSITEIT MAASTRICHT (NL423 - Zuid-Limburg) (Netherlands), WEIZMANN INSTITUTE OF SCIENCE (NoRegion - NoRegion) (Israel), BIOKINE THERAPEUTICS LTD (NoRegion - NoRegion) (Israel), EPSILON-BIOTECH BVBA (BE221 - Arr. Hasselt) (Belgium), GENMAB A/S (DK001 - København og Frederiksberg kommuner) (Denmark), IMMUNID SAS (FR714 - Isère) (France), OMRIX BIOPHARMACEUTICALS LTD (NoRegion - NoRegion) (Israel), REGULON AE (GR300 - Attiki) (Greece)

Autoimmune Myasthenia Gravis (MG) is a rare, chronic and heterogeneous neuromuscular disease characterised by severe muscle weakness. In most patients it is due to auto-antibodies to the acetylcholine receptor (AChR). The detrimental effects of the autoimmune attack on the muscle are not fully understood. The current treatments of MG induce severe side-effects with no permanent clinical remission. The early-onset patients are mostly females with thymic hyperplasia, while the existing experimental model for MG (EAMG) does not present thymic pathology. This proposal intends to develop models to progress in knowledge, monitoring, diagnosis and therapy of MG: a) Videomicroscopic models to explore the motility of lymphocytes involved in thymic remodelling in young females b) New transgenic models overexpressing CXCL13 chemokine in the thymus, to better mimic the human disease which involves thymic abnormalities c) Mouse model of estrogen deficiency, to determine the influence of estrogens in predisposition and progression of MG d) Humanized NOD/SCID mouse model transferred with human MG thymocytes to test therapy by human regulatory T cells e) TCR based signature, for better classification and monitoring of MG patients f) Rat EAMG models immunized with Torpedo AChR, to test an array of therapies (IVIg subfractions, chemokine inhibitors, regulatory cells g) Rat models immunized with recombinant human AChR subunits, to determine the contribution of each subunit to the pathogenicity and develop immunotherapies h) Monkey models to test protective anti-AChR antibodies. This research conducted by 4 academic and 6 SME partners has the potential to develop new commercial products for the benefit of the patients. Since the research teams of this program participate in a large "European MG Network" supported by the EC, interactions between the two networks will promote efficient dissemination of the obtained knowledge.

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