White matter disease: A novel approach to treatment of neuromyelitis optica.

摘要

A nonpathogenic monoclonal antibody might hold the key to successful treatment of neuromyelitis optica (NMO) -an autoimmune demyelinating disease characterized by lesions in the optic nerve and spinal cord. In Annals of Neurology, Alan Verkman, Jeffrey Bennett and colleagues present a novel approach that targets the interaction between the NMO autoantibody (NMO-Ig) and its antigen, aquaporin-4 (AQP4)."My group was responsible for the identification of the target of the NMO antibody in 1994" says Verkman. "NMO-Ig is very likely pathogenic by a mechanism involving astrocyte damage, which initiates a cascade of inflammation resulting in myelin loss and neurological deficit."In the new study, AQP4-specific recombinant antibodies were cloned from the cerebrospinal fluid of patients with NMO. The researchers identified an antibody that bound with high affinity to AQP4, and they mutated the Fc portion of this antibody to eliminate its effector functions, thereby rendering it nonpathogenic.