Cd38 modulated chemotaxis

C - Chemistry – Metallurgy – 12 – Q

Patent

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Details

C12Q 1/34 (2006.01) C07H 21/04 (2006.01) C07K 14/435 (2006.01) C12N 9/24 (2006.01) C12P 21/06 (2006.01) G01N 33/48 (2006.01)

Patent

CA 2424643

The present invention relates to methods for modulating the migratory activity of cells expressing CD38 for the treatment of disorders including, but not limited to, inflammation, ischemia, asthma, autoimmune disease, diabetes, arthritis, allergies, infection with pathogenic organisms and transplant rejection. Such cells include, for example, neutrophils, lymphocytes, eosinophils, macrophages and dentritic cells. The invention further relates to drug screening assays designed to identify compounds that modulate the ADP- ribosyl cyclase activity of CD38 and the use of such compounds in the treatment of disorders involving CD38 modulated cell migration. The invention is based on the discovery that CD38 ADP-ribosyl cyclase activity is required for chemotaxis. Furthermore, the invention relates to methods for identifying compounds that modulate the enzyme activity of the S. mansoni CD38 homologue and using those compounds in the treatment of pathologic disorders caused by helminth infection. This is based on the discovery that helminths such as S. mansoni express CD38 homologues.

La présente invention concerne des méthodes qui permettent de moduler l'activité migratrice des cellules exprimant le gène CD38 pour traiter des troubles comme, mais non limités à, l'inflammation, l'ischémie, l'asthme, la maladie auto-immune, le diabète, l'arthrite, les allergies, une infection dûe à des organismes pathogènes et le rejet de greffe. De telles cellules comprennent, par exemple, des polynucléaires neutrophiles, des lymphocytes, des polynucléaires eosinophiles, des macrophages et des cellulles dendritiques. L'invention concerne en outre des tests de criblage de médicaments, destinés à identifier les composés qui modulent l'activité l'ADP-ribosyl cyclase du CD38 et l'utilisation de tels composés dans le traitement de troubles impliquant la migration cellulaire modulée du CD38. Ladite invention repose sur la découverte du fait que l'activité de l'ADP-ribosyl cyclase du CD38 est nécessaire à la chimiotaxie. En outre, ladite invention concerne des procédés d'identification de composés qui modulent l'activité enzymatique de l'homologue du gène CD38 du S. mansoni et permettent d'utiliser ces composés dans le traitement de troubles pathologiques causés par une infection helminthe. Cette invention repose sur la découverte du fait que les helminthes tels le S. mansoni expriment des homologues du gène CD38.

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