title: Insights into the Mechanisms of the Therapeutic Efficacy of Alemtuzumab in Multiple Sclerosis.
abstract: The pathogenesis of multiple sclerosis (MS) is thought to involve peripheral activation of immune cells against central nervous system (CNS) antigens and their migration across the blood-brain barrier, leading to CNS inflammation and neurodegeneration. Alemtuzumab, a humanized anti-CD52 monoclonal antibody that rapidly depletes CD52-expressing cells from the circulation, is being investigated as a new treatment option in relapsing-remitting MS (RRMS). Clinical and radiologic results indicate robust suppression of inflammation related to the depletion of T and B lymphocytes during each treatment course of alemtuzumab. Furthermore, several lines of evidence suggest that the long-term clinical effects of alemtuzumab are attributable to qualitative changes in repopulating lymphocyte subsets potentially leading to a rebalancing of the immune system. Here, we review the contribution of data from animal models,ex vivohuman studies, and clinical trials to the understanding of the mechanisms underlying the therapeutic effect of alemtuzumab in patients with RRMS.
authors.affiliation: University of Ottawa, Multiple Sclerosis Research Clinic, the Ottawa Hospital-General Campus, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.affiliation: Genzyme, a Sanofi Company, Framingham, MA 01701, USA.
authors.forename: Johanne M
authors.initials: JM
authors.lastname: Kaplan
authors.affiliation: Department of Neurology, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599-7025, USA.
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
keywords: Alemtuzumab; Efficacy; Mechanism of action; Multiple sclerosis; Safety