Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside

Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, 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, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.