title: Therapeutic strategies targeting B-cells in multiple sclerosis.
abstract: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T-cells. Increasing evidence, however, suggests the fundamental role of B-cells in the pathogenesis of the disease. Recent strategies targeting B-cells in MS have demonstrated impressive and sometimes surprising results: B-cell depletion by monoclonal antibodies targeting the B-cell surface antigen CD20 (e.g. rituximab, ocrelizumab, ofatumumab) was shown to exert profound anti-inflammatory effect in MS with favorable risk-benefit ratio, with ocrelizumab demonstrating efficacy in both relapsing-remitting (RR) and primary-progressive (PP) MS in phase III clinical trials. Depletion of CD52 expressing T- and B-cells and monocytes by alemtuzumab resulted in impressive and durable suppression of disease activity in RRMS patients. On the other hand, strategies targeting B-cell cytokines such as atacicept resulted in increased disease activity. As our understanding of the biology of B-cells in MS is increasing, new compounds that target B-cells continue to be developed which promise to further expand the armamentarium of MS therapies and allow for more individualized therapy for patients with this complex disease.
authors.affiliation: Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: ronm@bmc.gov.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C533411:ocrelizumab
keywords: B-cells; CD20; Multiple sclerosis; Ocrelizumab