Multiple Sclerosis: Immunopathology and Treatment Update

Abstract

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.

The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

“…Various studies have illustrated the role of TGF-β1 in inciting the production of IL-10 [32,37,38], and also, it has become elucidated that TGF-β1 can trigger IL-10 through Smad4 pathway [16]. Following the same issue, TGF-β1 could repress the differentiation of naive CD4+ T cells into pathogenic Th17 ones and down-regulate the mRNA expression of IL-17 due to the immunosuppressive traits [39][40][41]. However, there are contradictory results about the impact of TGF-β1 on the differentiation of Th17 to IL-17 in a way that some of them indicated that TGF-β1 was able to trigger the differentiation of Th17 to IL-17 [42,43].…”

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

“…Interferon beta formulations were the first DMTs approved for the treatment of RMS (Dargahi et al, 2017). Peginterferon beta-1a was developed by covalently attaching a polyethylene glycol side chain to interferon beta-1a (Kieseier and Calabresi, 2012).…”

Microglia suppress the secondary progression of autoimmune encephalomyelitis

“…However, 50–70% of RRMS patients become chronic and develop secondary progressive MS (SPMS), which is characterized by continuous progression (Rovaris et al, ). Although previous studies identified the pathological mechanism of RRMS and developed treatments to prevent relapsing (Dargahi et al, ), the pathological mechanism of SPMS remains poorly understood. Therefore, it is necessary to elucidate the pathological molecular mechanism associated with SPMS in order to develop a therapeutic strategy.…”