L'utilisation de CD154 modifié dans le traitement de l'arthrite rhumatoïde et ses complications thrombotiques.

 

Walid Mourad

Centre de recherche du CHUM

 

Domaine : appareil locomoteur et arthrite

Programme Fonds d'innovation Pfizer-FRQS

Concours 2012-2013

Partenaire

Pfizer Canada

Rheumatoid arthritis (RA) is an autoimmune disease affecting 1% of the world's population. It is characterized by a chronic inflammation in tissues of the joints, leading to their progressive damage. Interestingly, RA conditions are shown to be associated with vascular diseases, such as thrombosis (clot formation inside the blood vessel), whereby RA patients exhibit an increased morbidity and mortality rates due to vascular complications, as compared to the general population.

CD154 is an inflammatory molecule that has been implicated in the pathogenesis of both RA and vascular conditions. CD154 was initially thought to bind only one receptor, CD40. However, recent evidence from several groups including ours demonstrated that CD154 binds and induce inflammatory functions via three more receptors, all belonging to the family of integrins. Interestingly, the role of CD154 in inflammatory diseases such as RA and vascular diseases has allowed the development of therapeutic strategies involving CD154 interactions. However existing therapeutic regimens targeted only CD154 interactions with its classical receptor, without considering the recently described receptors. Based on years of investigations, we generated novel molecules of CD154 with altered interaction capacities with the various receptors. The therapeutic efficacy of these molecules will be evaluated in RA and thrombosis conditions, using animal models of the diseases.

Data generated herein will outline the role of particular CD154 receptor(s) in RA and associated thrombosis and will pave the way for the identification of a novel therapeutic tool for the prevention/treatment of RA and associated thrombosis.