title: The role of laquinimod in modulation of the immune response in relapsing-remitting multiple sclerosis: Lessons from gene expression signatures.
abstract: Laquinimod, is a potential oral immunomodulatory drug, for relapsing-remitting multiple sclerosis (RRMS). We analyzed the blood-transcriptional changes in RRMS patients (who participated in the ALLEGRO clinical trial) at one and six months after laquinimod treatment using gene expression microarrays. The molecular effects of laquinimod were enhanced by duration of treatment and showed down-regulation of inflammatory responses mainly via TGFb signaling, and of pro-inflammatory cytokines as well as of cellular movement, including adhesion, migration and leukocyte extravasation signaling. Our results demonstrate that laquinimod suppresses inflammation through down-regulation of inflammatory cytokines and arrest of leukocyte extravasation and thereby could attenuate disease activity in RRMS patients.
authors.affiliation: Multiple Sclerosis Center, Neurogenomic Laboratory, Sheba Medical Center, Israel. Electronic address: rina.falb@sheba.health.gov.il.
authors.forename: R
authors.initials: R
authors.lastname: Zilkha-Falb
authors.affiliation: Multiple Sclerosis Center, Neurogenomic Laboratory, Sheba Medical Center, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Gurevich
authors.affiliation: Teva Pharmaceutical Industries Ltd., 5 Bazel Street, Petah Tiqva 49131, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Hayardeny
authors.affiliation: Multiple Sclerosis Center, Neurogenomic Laboratory, Sheba Medical Center, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Achiron
mesh_terms: D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000097:blood; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000235:genetics
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D016328:NF-kappa B; D015363:Quinolones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C476223:laquinimod
keywords: Gene expression microarray; Laquinimod; Multiple sclerosis; Peripheral blood mononuclear cells