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pathways that are important in eliminating microbes. inhibitory effect on migration of neutrophils and
C1 is only involved in the classical pathway; reductive effect on neutrophil-related tissue damages
[47]
inhibition C1 not only blocks the cytotoxicity in a NMO model of mouse. The authors further
(CDC) and antibody-dependent cellular cytotoxicity observed that neutrophils enter the CNS within 24 h
[47]
（ADCC） effect, but also saves the anti-infection after onset, suggesting that Sivelestat may be effective
function of the alternative and lectin pathway. It in the treatment of acute NMO.
has been discovered that C1-inhibiting monoclonal
antibody is sufficient for preventing NMO in mouse Eosinophils infiltration into the demyelinating lesions is
[48]
models. [33] Another small-scale phase I clinical trial another pathological hallmark of NMO. Degranulation
reported C1 esterase inhibitor significantly reduced of mouse bone marrow-derived eosinophils significantly
the EDSS score of patients with NMO, and no obvious enhanced the AQP4-IgG-mediated ADCC and CDC effect
side effects showed up. [34] So the selective inhibition in cultured spinal cord slices, indicating eosinophils
of the classical complement pathway is hypothesized granules are involved in the pathogenic process of
[48]
as another more promising and safer complement- NMO. In the same study, cetirizine, the second
targeted therapy. generation of antihistamine, reduces tissue damage in a
NMO model of mouse, which may be another option to
Inhibition of IL-6-IL-6 receptor signaling control NMO. [48]
A few studies have indicated that interleukin 6
(IL-6), increasing in NMO during relapse phase, is CONCLUSION
a potent driver of NMO relapsing to enhance the Corticosteroids, azathioprine, mycophenolate mofetil
survival of plasma blast and secretion of AQP4- and rituximab are still the first-line therapy for
IgG. [15,35-37] Tocilizumab, an IL-6 receptor blocking NMO. With the dramatically increasing knowledge
antibody, reduced the survival of AQP4-IgG- of NMO, a variety of novel therapies are under test
secreting plasma blast and reduced NMO relapse. and development, including complement-targeted
A few case reports showed that tocilizumabhasa therapy, IL-6 targeted therapy, restoring the stability
positive impact on the patients’ condition due to its of BBB and granulocytes inhibition, etc. The ultimate
ability of suppressing the CD20-plasma cells and goal of NMO therapeutics is to develop a highly
decreasing the titer of AQP4-IgG, [38-40] suggesting selective, low side effect therapy. This is challenging
tocilizumab is a promising alternative therapy for since clinical experience of treating NMO, a rare
aggressive, immunosuppressive agents-refractory disease, is limited. So multiple-center, large-scale
patients. Clinical trials in large scale are needed to randomized controlled trials for treatment-naïve
examine the effectiveness and safety of tocilizumab patients are needed to review the efficacy of these
in NMO treatment. therapeutic approaches.

Restoring stability of blood brain barrier Acknowlegments
Elevated level of albumin was detected in the CSF This work was supported by the New Clinical Technique
of patients with NMO during relapse, indicating the or Program of Tangdu Hospital in 2013 and 2014.
stability of BBB is damaged in the acute phase of
[41]
NMO. A few studies reported serum from AQP4-IgG Financial support and sponsorship
positive patients increases the permeability of artificial Nil.
BBB and reduces the expression of tight junction
proteins. [42,43] Although the specific mechanism still Conflicts of interest
remains unclear, majority of studies strongly suggested There are no conflicts of interest.
that the vascular endothelial growth factor (VEGF) [42]
and matrix metalloproteinases were involved. REFERENCES
[44]
Currently the anti-VEGF monoclonal antibody, 1. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF,
bevacizumab, is under clinical review of the clinical Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody
benefits in restoring the stability of BBB in NMO marker of neuromyelitis optica: distinction from multiple sclerosis.
Lancet 2004;364:2106-12.
patients. [45] 2. Cabre P, Heinzlef O, Merle H, Buisson GG, Bera O, Bellance R,
Vernant JC, Smadja D. MS and neuromyelitis optica in Martinique
Restraining the activity of neutrophils 3. (French West Indies). Neurology 2001; 56:507-14.
Cabrera-Gomez JA, Kurtzke JF, Gonzalez-Quevedo A, Lara-
Large number of neutrophils was detected in the Rodriguez R. An epidemiological study of neuromyelitis optica in
perivascular lesions in both human cases of [46] and Cuba. J Neurol 2009;256:35-44.
animal model of NMO. Sivelestat, a neutrophil 4. Asgari N, Lillevang ST, Skejoe HP, Falah M, Stenager E, Kyvik KO.
[47]
A population-based study of neuromyelitis optica in Caucasians.
protease inhibitor, has been demonstrated with the Neurol 2011;76:1589-95.

130 Neuroimmunol Neuroinflammation | Volume 3 | June 20, 2016