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Review
. 2017 Mar 24:7:47-60.
doi: 10.2147/DNND.S71986. eCollection 2017.

Advances in the treatment of relapsing-remitting multiple sclerosis: the role of pegylated interferon β-1a

Kendra L Furber  1   2   3 , Marina Van Agten  1   2   3 , Charity Evans  2   4 , Azita Haddadi  2 , J Ronald Doucette  3   4   5 , Adil J Nazarali  1   2   3   4
Affiliations
Review

Advances in the treatment of relapsing-remitting multiple sclerosis: the role of pegylated interferon β-1a

Kendra L Furber et al. Degener Neurol Neuromuscul Dis. .

Abstract

Multiple sclerosis (MS) is a progressive, neurodegenerative disease with unpredictable phases of relapse and remission. The cause of MS is unknown, but the pathology is characterized by infiltration of auto-reactive immune cells into the central nervous system (CNS) resulting in widespread neuroinflammation and neurodegeneration. Immunomodulatory-based therapies emerged in the 1990s and have been a cornerstone of disease management ever since. Interferon β (IFNβ) was the first biologic approved after demonstrating decreased relapse rates, disease activity and progression of disability in clinical trials. However, frequent dosing schedules have limited patient acceptance for long-term therapy. Pegylation, the process by which molecules of polyethylene glycol are covalently linked to a compound, has been utilized to increase the half-life of IFNβ and decrease the frequency of administration required. To date, there has been one clinical trial evaluating the efficacy of pegylated IFN. The purpose of this article is to provide an overview of the role of IFN in the treatment of MS and evaluate the available evidence for pegylated IFN therapy in MS.

Keywords: disease-modifying therapy; interferon; multiple sclerosis; pegylation; relapsing–remitting.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic depicting the role of PEG-IFNβ therapy in MS. Notes: (A) In MS, pro-inflammatory cytokines stimulate CD4+ cells to proliferate and differentiate into Th1 and Th17 effector cells. Activated T cells express VLA-4, which interacts with VCAM-1 on endothelial cells, to facilitate crossing the BBB. In the CNS, auto-reactive T cells and macrophages result in damage to the myelin sheath, axons and neurons. Inflammatory demyelinating lesions result in the clinical presentation of MS. (B) IFNβ is conjugated to PEG to increase the molecule’s serum concentration and half-life. Proposed actions of IFNβ include modulating cytokine milieu to favor anti-inflammatory pathways, which inhibits expansion of Th1/Th17 and promotes expansion of Th2 cells. Down-regulation of VLA-4 and inhibition of MMP-9 reduce migration of activated T cells into CNS. (C) Linking of anti-VCAM-1 antibodies to the PEG tail may enhance IFNβ anti-inflammatory actions by 1) blocking interaction of leukocytes expressing VLA-4 with VCAM-1 and 2) increasing local concentration of PEG-IFNβ at BBB. Abbreviations: BBB, blood–brain barrier; CNS, central nervous system; IFNβ, interferon beta; M, macrophage; MMP, matrix metalloproteinase; MS, multiple sclerosis; PEG, polyethylene glycol; PEG-IFNβ, pegylated interferon β; TIMP-1, tissue inhibitor of metalloproteinase-1; VCAM-1, vacular cell adhesion molecule 1; VLA-4, very late activation antigen-4.
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