ArticleAnnals of neurology2012
Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 254 citations in OpenAlex.
- Dynamic characterization of pathological and functional deterioration in a mouse model of optic neuritis related to neuromyelitis optica spectrum disorder.Neural regeneration research · 2026Article
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Natalizumab exacerbates astrocytopathy in NMOSD via blockade of endothelial VCAM1-astrocytic integrin α4 interaction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dissecting NMOSD pathogenesis through animal models: a mechanism-oriented systems perspective.Frontiers in immunology · 2026Review
- Aquaporin-4 in Stroke and Brain Edema-Friend or Foe?International journal of molecular sciences · 2025Review
- Emerging Role of Targeted Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Complement inhibition rapidly blocks lesion extension and facilitates remyelination in neuromyelitis optica.Acta neuropathologica communications · 2025Article
- Exploring Aquaporins in Human Studies: Mechanisms and Therapeutic Potential in Critical Illness.Life (Basel, Switzerland) · 2024Review
- The role of Aquaporins in tumorigenesis: implications for therapeutic development.Cell communication and signaling : CCS · 2024Review
- Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice.Fluids and barriers of the CNS · 2024Article
- Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management.Journal of neurology · 2024Review
- Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology.Acta neuropathologica · 2023Article
- Aquaporins in Nervous System.Advances in experimental medicine and biology · 2023Article
- Optic Neuritis in Multiple Sclerosis-A Review of Molecular Mechanisms Involved in the Degenerative Process.Current issues in molecular biology · 2022Review
- Review
- Treatment and Relapse Prevention of Typical and Atypical Optic Neuritis.International journal of molecular sciences · 2022Review
- Next-generation antibody-based therapies in neurology.Brain : a journal of neurology · 2022Review
- Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System.Biomolecules · 2022Review
- Aquaporins in Cancer Biology.Frontiers in oncology · 2022Review
- Cytoprotective IgG antibodies in sera from a subset of patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder.Scientific reports · 2021Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveNeuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system. Circulating autoantibodies (NMO-immunoglobulin [Ig]G) against astrocyte water channel aquaporin-4 (AQP4) cause complement- and cell-mediated 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-IgG binding to its target, AQP4.
methodsWe generated nonpathogenic recombinant monoclonal anti-AQP4 antibodies that selectively block NMO-IgG binding to AQP4. These antibodies comprise a tight-binding anti-AQP4 Fab and a mutated Fc that lacks functionality for complement- and cell-mediated cytotoxicity. The efficacy of the blocking antibodies was studied using cell culture, spinal cord slice, and in vivo mouse models of NMO.
resultsIn AQP4-expressing cell cultures, the nonpathogenic competing antibodies blocked binding of NMO-IgG in human sera, reducing to near zero complement- and cell-mediated 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.
interpretationOur 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.