Treatment of neuromyelitis optica spectrum disorder: revisiting the complement system and other aspects of pathogenesis

Summary Neuromyelitis optica spectrum disorder (NMOSD) represents a rare neuroimmunological disease causing recurrent attacks and accumulation of permanent disability in affected patients. The discovery of the pathogenic IgG‑1 antibody targeting a water channel expressed in astrocytes, aquaporin 4, constitutes a milestone achievement. Subsequently, multiple pathophysiological aspects of this distinct disease entity have been investigated. Demyelinating lesions and axonal damage ensue from autoantibodies targeting an astroglial epitope. This conundrum has been addressed in the current disease model, where activation of the complement system as well as B cells and interleukin 6 (IL-6) emerged as key contributors. It is the aim of this review to address these factors in light of novel treatment compounds which reflect these pathophysiological concepts in aiming for attack prevention, thus reducing disease burden in patients with NMOSD.