USE OF GUANABENZ OR DERIVATES THEREOF FOR THE TREATMENT OF TYPE I IFN-DEPENDENT PATHOLOGIES

摘要

The present invention relates to the use of Guanabenz or derivates thereof for the treatment of type I IFN-dependent pathologies. The inventors investigate here how pharmacological interference with the eIF2α-P pathway can be beneficial for the treatment of immune pathological conditions. Using both mouse and human DCs, as well as B cells, they show that GBZ prevents endosomal toll-like-receptor 9 (TLR9) activation by CpG ODN or DNA-Immunoglobulin complexes, as well as TLR3, TLR7 and RIG-I like receptors (RLR, RIG-I or MDA5), by RNAs or small compounds. In vivo, GBZ treatment protects mice from CpG-dependent cytokine shock and decreases anti-nucleic acid auto-antibodies production in the TMPD-induced systemic lupus erythematosus model. The present invention thus relates to a method of treating a type I IFN-dependent pathology in a subject comprising administering the subject with Guanabenz or a derivative thereof.