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Zhang et al. Neuroimmunol Neuroinflammation 2019;6:8 I http://dx.doi.org/10.20517/2347-8659.2019.06 Page 9 of 16

Figure 1. Pathogenesis of multiple sclerosis and targets of drug action. ① Reduced production of Th1 and Th17 cells and Th1-Th2 shift
(interferon-β, teriflunomide, dimethyl fumarate); ② Competitive binding of MHC class II molecules (glatiramer acetate); ③ Depletion
of CD20-positive lymphocytes (ocrelizumab, rituximab); ④ Regulation of T-cells, B-cells, NK cells, and dendritic cells (interferon-b, glatiramer
acetate); ⑤ Depletion of CD52-positive lymphocytes (alemtuzumab); ⑥ Alteration of lymphocyte distribution (fingolimod); ⑦ Preventing
activated CD4+ T-cells from crossing the blood-brain barrier (natalizumab, interferon-β); ⑧Promoting leukocyte migration to the central nervous
system (glatiramer acetate). VLA-4: very late antigen-4; MMP: matrix metalloproteinase; MHC: major histocompatibility complex; IFN:
interferon; IL: interleukin; NK: natural killer; TCR: T-cell receptor; Th: T helper

rituximab to prevent complications [188,189] . Other immunosuppressants that have been used to treat NMOSD
include tacrolimus, cyclophosphamide, methotrexate, and cyclosporin A. Tacrolimus and cyclosporin A
produce good selective inhibition of Th cells, and methotrexate inhibits folate metabolism. However, these
drugs have not been used frequently because of their uncertain effects [84-86] . Some studies have found that
some new DMDs for MS, such as fingolimod, DMF, alemtuzumab, and natalizumab, may cause the disease
to worsen, mainly in patients with AQP4-IgG-positive NMOSD [190-194] . There are insufficient data to support
or discourage the use of GA and IFN-β in NMOSD [195,196] . Currently, experience in the treatment of MOG-
IgG-positive NMOSD is still lacking, and long-term immunosuppression may be effective [197,198] .

CONCLUSION
Currently, MS and NMOSD are incurable diseases. There is no consensus on the best treatment strategy or
treatment target. Early, conventional immunosuppressive agents, such as azathioprine and cyclophosphamide,
have been used for the treatment of MS and NMOSD. Various immunosuppressive agents have different
degrees of efficacy in MS or NMOSD. Among them, only azathioprine and mycophenolate mofetil are
currently recommended for the treatment of NMOSD, but no credible randomized controlled trial has yet
proved their effects. Now, more than a dozen DMDs are available for MS, with varying levels of efficacy and
safety. Immunomodulators against MS have been marketed since 1993, and conventional immunosuppressive
agents have rarely been used in this condition. Compared with new immunomodulators, conventional
immunosuppressants have more side effects and worse drug targeting. However, in some countries and
regions, due to economic reasons or a lack of DMDs, cyclophosphamide, tacrolimus, and other drugs are still
used to treat MS and have some therapeutic effect [199-201] . Despite the use of DMDs, some patients still have
exacerbations and develop progressive disease. Few DMDs are available for NMOSD, and there is a lack of