Atacicept: targeting B cells in multiple sclerosis

Multiple sclerosis (MS) has traditionally been considered to be a T-cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatments directed against B cells. In this paper...

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Main Authors: Hans-Peter Hartung, Bernd C. Kieseier
Format: Article
Language:English
Published: SAGE Publishing 2010-07-01
Series:Therapeutic Advances in Neurological Disorders
Online Access:https://doi.org/10.1177/1756285610371146
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author Hans-Peter Hartung
Bernd C. Kieseier
author_facet Hans-Peter Hartung
Bernd C. Kieseier
author_sort Hans-Peter Hartung
collection DOAJ
description Multiple sclerosis (MS) has traditionally been considered to be a T-cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatments directed against B cells. In this paper we summarize evidence for the key role of B cells in the immunopathology of MS and review data supporting the use of a novel B-cell targeted therapy, atacicept, in this condition. Atacicept is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B-cell maturation, function and survival. Atacicept has shown selective effects on cells of the B-cell lineage, acting on mature B cells and blocking plasma cells and late stages of B-cell development while sparing B-cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. Clinical studies were initiated to investigate the safety, tolerability and efficacy of atacicept in patients with MS. An unexpected increase in inflammatory activity in one of the trials, however, led to suspension of all atacicept trials in MS.
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spelling doaj.art-023750bdd4014f28a485d4a94bc3ab4f2022-12-22T00:28:34ZengSAGE PublishingTherapeutic Advances in Neurological Disorders1756-28562010-07-01310.1177/1756285610371146Atacicept: targeting B cells in multiple sclerosisHans-Peter HartungBernd C. KieseierMultiple sclerosis (MS) has traditionally been considered to be a T-cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatments directed against B cells. In this paper we summarize evidence for the key role of B cells in the immunopathology of MS and review data supporting the use of a novel B-cell targeted therapy, atacicept, in this condition. Atacicept is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B-cell maturation, function and survival. Atacicept has shown selective effects on cells of the B-cell lineage, acting on mature B cells and blocking plasma cells and late stages of B-cell development while sparing B-cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. Clinical studies were initiated to investigate the safety, tolerability and efficacy of atacicept in patients with MS. An unexpected increase in inflammatory activity in one of the trials, however, led to suspension of all atacicept trials in MS.https://doi.org/10.1177/1756285610371146
spellingShingle Hans-Peter Hartung
Bernd C. Kieseier
Atacicept: targeting B cells in multiple sclerosis
Therapeutic Advances in Neurological Disorders
title Atacicept: targeting B cells in multiple sclerosis
title_full Atacicept: targeting B cells in multiple sclerosis
title_fullStr Atacicept: targeting B cells in multiple sclerosis
title_full_unstemmed Atacicept: targeting B cells in multiple sclerosis
title_short Atacicept: targeting B cells in multiple sclerosis
title_sort atacicept targeting b cells in multiple sclerosis
url https://doi.org/10.1177/1756285610371146
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