Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside
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REVIEW
Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside Wenli Zhu1,2 • Yaling Zhang1 • Zhen Wang1 • Ying Fu1 • Yaping Yan1
Received: 8 December 2019 / Accepted: 10 April 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
Abstract Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibodymediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of [60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, bloodbrain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy
& Yaping Yan [email protected] 1
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an 710119, China
2
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China
of mAb trials in NMOSD, including preclinical and experimental investigations. Keywords Neuromyelitis optica spectrum disorders Monoclonal antibody AQP4-IgG Astrocyte Central nervous system
Introduction Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a devastating autoimmune inflammatory disease of the central nervous system (CNS), with a predilection for causing lesions in the optic nerve and spinal cord [1–3]. NMO was previously considered a subtype of multiple sclerosis (MS); however, the discovery of an autoantibody against aquaporin-4 (AQP4), the dominant water channel which is strongly expressed on astrocyte end-feet, distinguishes NMO from MS and helps to establish a diagnosis of NMO [1, 4]. It is pertinent to distinguish between MNO and MS at diagnosis, as some MS therapies, such as natalizumab and interferon-b, aggravate rather than treat NMO [5, 6]. Autoantibodies against AQP4 (AQP4–IgG), which are present in the large majority of NMO patients, function directly in the pathogenesis of disease [7, 8]. In 2015, the Wingerchuck criteria, an international
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