Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.

Optic Neuropathies: Current and Future Strategies for Optic Nerve Protection and Repair

“…Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. The review by Huang et al [ 9 ] is intended to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.…”

Neuromyelitis optica spectrum disorders (NMOSD) and systemic lupus erythematosus (SLE): Dangerous duo

“…[2][3][4] In NMOSD, pathophysiology is mediated by the AQP4 immunoglobulins (IgGs) that enter the CNS via the blood-brain barrier (BBB) and selectively bind to the astrocytic water channel protein aquaporin 4 (AQP4) at the endfeet of astrocytes [Figure 1]. 1,4 AQP4 normally maintains water homeostasis and helps mediate waste protein clearance. AQP4-antibody is mainly of the immunoglogulin G1 (IgG) type which activates complement efficiently.…”

“…Firstly, common genetic and /or environmental factors predisposing to autoimmune rheumatic disease could explain the co-occurrence. 1,4,[7][8][9]17 Secondly, the initial autoimmune rheumatic disease may contribute (via inflammatory mediators and autoantibodies) to the disruption of the BBB allowing the AQP4 autoantibodies to gain access to the CNS and lead to the clinical manifestations of NMO. 1,4,[7][8][9] The coexistence of NMO and SLE remains rare and explicit evidence-based guidelines for the management of such cases are still lacking.…”

“…4,21,24 Moreover, AZA and MMF have been widely used, while corticosteroids, mitoxantrone, cyclosporine, and cyclophosphamide can also be considered. 1,4,21 Table 2 depicts the most common maintenance medications used for NMOSD.…”

“…Treatments remained "empiric" as randomized clinical trials have only recently been conducted. 1,21,24 Since 2019, the therapeutic landscape for NMOSD has been transformed with the introduction of more targeted therapy and with the FDA approval of 3 new drugs namely Eculizumab (terminal complement protein C5 inhibitor), Inebilizumab (CD-19 directed cytolytic antibody) and Satralizumab (IL-6 inhibitor) all demonstrating robust benefits in preventing relapses. 1,4,25 Modulation of the complement system in the treatment of NMOSD was proposed with Eculizumab which was the first FDAapproved treatment for adults with AQP4 antibody-positive NMOSD.…”