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Atacicept bei Multipler Sklerose

Ein neuer B-Lymphozyten-gerichteter Therapieansatz

Atacicept: a new B lymphocyte-targeted therapy for multiple sclerosis

 

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Zusammenfassung

Die Multiple Sklerose (MS) gilt traditionell als eine von T-Lymphozyten vermittelte Erkrankung. Allerdings spricht immer mehr für eine kritische Beteiligung von B-Lymphozyten und Autoantikörpern am pathologischen Geschehen bei der MS. Somit liegt es nahe, gegen B-Zellen gerichtete Therapieansätze zu verfolgen. In dieser Arbeit werden zunächst die für eine Schlüsselrolle der B-Zellen bei der Immunpathologie der MS sprechenden Erkenntnisse zusammengefasst und anschließend die Datenlage zur Anwendung von Atacicept, einer neuen B-Lymphozyten-gerichteten Therapiemöglichkeit bei MS, vorgestellt und kritisch gewürdigt. Bei Atacicept handelt es sich um ein humanes rekombinantes Fusionsprotein, das unter anderem aus demjenigen Teil eines bestimmten Rezeptors besteht, an den die Zytokine BLyS („B-lymphocyte stimulator“) und APRIL („A proliferation-inducing ligand“) andocken. BlyS und APRIL sind wichtige Regulatoren der Reifung, Funktion und Überlebensdauer von B-Zellen. Atacicept zeigt selektive Wirkungen auf bestimmte Zellen der B-Lymphozyten-Zellreihe. So wirkt Atacicept auf reife B-Zellen und blockiert Plasmazellen sowie späte Stadien der B-Zell-Entwicklung, während die B-Lymphozyten-Vorläuferzellen und Gedächtnis-B-Zellen unbeeinflusst bleiben. Bereits nachgewiesen sind die Wirksamkeit von Atacicept in Tiermodellen von Autoimmunerkrankungen und die biologische Aktivität von Atacicept bei Patienten mit systemischem Lupus erythematodes (SLE) und rheumatoider Arthritis (RA). In derzeit laufenden klinischen Studien werden Sicherheit, Verträglichkeit und Wirksamkeit von Atacicept bei Patienten mit MS, SLE und RA untersucht.

Summary

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 treatment strategies directed against B cells. This paper summarizes the evidence for a key role of B cells in the immunopathology of MS and reviews data supporting the use of a novel B cell-targeted therapy, atacicept, for 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. Ongoing clinical studies are investigating the safety, tolerability and efficacy of atacicept in patients with MS, SLE and RA.

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Danksagung

Der Autor bedankt sich bei Frau Dr. Andrea Plant PhD (Caudex Medical) für die technische Hilfe bei der Erstellung des Manuskripts, Herrn Dr. Norbert Zessack, MerckSerono für die kritische Durchsicht sowie Herrn PD Dr. Patrick Küry für die Hilfe bei der Erstellung der Abbildungen.

Interessenkonflikt

Der Autor hat nach Genehmigung durch den Rektor der HHU Honorare für Beratungen und Vortragstätigkeit von BayerScheringPharma; Biogen Idec; Bio MS; Genzyme; Merck Serono; Novartis; Teva Sanofi Aventis erhalten.

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  1. Neurologische Klinik, Heinrich-Heine-Universität, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    H.-P. Hartung

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Hartung, HP. Atacicept bei Multipler Sklerose. Nervenarzt 80, 1462–1472 (2009). https://doi.org/10.1007/s00115-009-2838-6

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