ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Small-molecule inhibitors of NMO-IgG binding to aquaporin-4 reduce astrocyte cytotoxicity in neuromyelitis optica.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Different Targets of Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders: A Meta-Analysis Evidenced From Randomized Controlled Trials.Frontiers in neurology · 2020Pooled it
- The IL-1β-STING Signaling Axis Drives Neuromyelitis Optica Pathogenesis in a Murine Model.Annals of neurology · 2026Article
- Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model.bioRxiv : the preprint server for biology · 2026Article
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications.Biomedicines · 2026Review
- Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica.Science advances · 2025Article
- TDP43 augments astrocyte inflammatory activity through mtDNA-cGAS-STING axis in NMOSD.Journal of neuroinflammation · 2025Article
- Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica.bioRxiv : the preprint server for biology · 2024Article
- ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.Molecules (Basel, Switzerland) · 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
- Monoclonal Antibody Therapies Beyond Complement for NMOSD and MOGAD.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Single-cell approaches to investigate B cells and antibodies in autoimmune neurological disorders.Cellular & molecular immunology · 2021Review
- Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside.Neuroscience bulletin · 2020Review
- Emerging therapeutic targets for neuromyelitis optica spectrum disorder.Expert opinion on therapeutic targets · 2020Review
- Affinity-matured 'aquaporumab' anti-aquaporin-4 antibody for therapy of seropositive neuromyelitis optica spectrum disorders.Neuropharmacology · 2020Article
- Experimental animal models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress and shortcomings.Brain pathology (Zurich, Switzerland) · 2020Review
- Cepharanthine: An update of its mode of action, pharmacological properties and medical applications.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2019Review
- Pharmacotherapy for Neuromyelitis Optica Spectrum Disorders: Current Management and Future Options.Drugs · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of spinal cord and optic nerve caused by pathogenic autoantibodies (NMO-IgG) against astrocyte aquaporin-4 (AQP4). We developed a high-throughput screen to identify blockers of NMO-IgG binding to human AQP4 using a human recombinant monoclonal NMO-IgG and transfected Fisher rat thyroid cells stably expressing human M23-AQP4. Screening of ∼60,000 compounds yielded the antiviral arbidol, the flavonoid tamarixetin, and several plant-derived berbamine alkaloids, each of which blocked NMO-IgG binding to AQP4 without affecting AQP4 expression, array assembly, or water permeability. The compounds inhibited NMO-IgG binding to AQP4 in NMO patient sera and blocked NMO-IgG-dependent complement- and cell-mediated cytotoxicity with IC(50) down to ∼5 μM. Docking computations identified putative sites of blocker binding at the extracellular surface of AQP4. The blockers did not affect complement-dependent cytotoxicity caused by anti-GD3 antibody binding to ganglioside GD3. The blockers reduced by >80% the severity of NMO lesions in an ex vivo spinal cord slice culture model of NMO and in mice in vivo. Our results provide proof of concept for a small-molecule blocker strategy to reduce NMO pathology. Small-molecule blockers may also be useful for other autoimmune diseases caused by binding of pathogenic autoantibodies to defined targets.
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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.