{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:18:36Z","timestamp":1790965116768,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,23]],"date-time":"2012-01-23T00:00:00Z","timestamp":1327276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective:<\/jats:title><jats:p>Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system. Circulating autoantibodies (NMO\u2010immunoglobulin [Ig]G) against astrocyte water channel aquaporin\u20104 (AQP4) cause complement\u2010 and cell\u2010mediated astrocyte damage with consequent neuroinflammation and demyelination. Current NMO therapies, which have limited efficacy, include immunosuppression and plasma exchange. The objective of this study was to develop a potential new NMO therapy based on blocking of pathogenic NMO\u2010IgG binding to its target, AQP4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>We generated nonpathogenic recombinant monoclonal anti\u2010AQP4 antibodies that selectively block NMO\u2010IgG binding to AQP4. These antibodies comprise a tight\u2010binding anti\u2010AQP4 Fab and a mutated Fc that lacks functionality for complement\u2010 and cell\u2010mediated cytotoxicity. The efficacy of the blocking antibodies was studied using cell culture, spinal cord slice, and in vivo mouse models of NMO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>In AQP4\u2010expressing cell cultures, the nonpathogenic competing antibodies blocked binding of NMO\u2010IgG in human sera, reducing to near zero complement\u2010 and cell\u2010mediated cytotoxicity. The antibodies prevented the development of NMO lesions in an ex vivo spinal cord slice model of NMO and in an in vivo mouse model, without causing cytotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation:<\/jats:title><jats:p>Our results provide proof of concept for a therapy of NMO with blocking antibodies. The broad efficacy of antibody inhibition is likely due to steric competition because of its large physical size compared to AQP4. Blocker therapy to prevent binding of pathogenic autoantibodies to their targets may be useful for treatment of other autoimmune diseases as well. 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