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Therapeutic strategies targeting B-cells in multiple sclerosis

Autoimmunity Reviews, Volume 15, Issue 7, July 2016, Pages 714–718

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.

Keywords: B-cells, Multiple sclerosis, CD20, Ocrelizumab.

Footnotes

Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Department of Neurology, Barzilai Medical Center, 2 Hahistadrut St., Ashkelon 7830604, Israel. Tel.: + 972 8 674 5117; fax: + 972 8 674 5463.