ArticlePloS one2014
Potential therapeutic benefit of C1-esterase inhibitor in neuromyelitis optica evaluated in vitro and in an experimental rat model.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
16 citing papers in PubMed, 24 citations in OpenAlex.
- Friend or foe: assessing the value of animal models for facilitating clinical breakthroughs in complement research.The Journal of clinical investigation · 2025Review
- Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies.Frontiers in neurology · 2025Review
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges.International journal of molecular sciences · 2023Review
- ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.Molecules (Basel, Switzerland) · 2023Article
- Anti-complement Agents for Autoimmune Neurological Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Targeting the complement system in neuromyelitis optica spectrum disorder.Expert opinion on biological therapy · 2021Review
- Targeting Neuromyelitis Optica Pathogenesis: Results from Randomized Controlled Trials of Biologics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here?Frontiers in immunology · 2020Review
- Experimental animal models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress and shortcomings.Brain pathology (Zurich, Switzerland) · 2020Review
- Contradictory to its effects on thrombin, C1-inhibitor reduces plasmin generation in the presence of thrombomodulin.Journal of thrombosis and thrombolysis · 2019Article
- CD55 upregulation in astrocytes by statins as potential therapy for AQP4-IgG seropositive neuromyelitis optica.Journal of neuroinflammation · 2019Article
- Pharmacotherapy for Neuromyelitis Optica Spectrum Disorders: Current Management and Future Options.Drugs · 2019Review
- Neuromyelitis Optica: Deciphering a Complex Immune-Mediated Astrocytopathy.Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society · 2017Review
- C1-inhibitor influence on platelet activation by thrombin receptors agonists.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system in which binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) to astrocytes causes complement-dependent cytotoxicity (CDC) and inflammation resulting in oligodendrocyte and neuronal injury. There is compelling evidence for a central role of complement in NMO pathogenesis. Here, we evaluated the potential of C1-esterase inhibitor (C1-inh) for complement-targeted therapy of NMO. C1-inh is an anti-inflammatory plasma protein with serine protease inhibition activity that has a broad range of biological activities on the contact (kallikrein), coagulation, fibrinolytic and complement systems. C1-inh is approved for therapy of hereditary angioedema (HAE) and has been studied in a small safety trial in acute NMO relapses (NCT 01759602). In vitro assays of NMO-IgG-dependent CDC showed C1-inh inhibition of human and rat complement, but with predicted minimal complement inhibition activity at a dose of 2000 units in humans. Inhibition of complement by C1-inh was potentiated by ∼10-fold by polysulfated macromolecules including heparin and dextran sulfate. In rats, intravenous C1-inh at a dose 30-fold greater than that approved to treat HAE inhibited serum complement activity by <5%, even when supplemented with heparin. Also, high-dose C1-inh did not reduce pathology in a rat model of NMO produced by intracerebral injection of NMO-IgG. Therefore, although C1r and C1s are targets of C1-inh, our in vitro data with human serum and in vivo data in rats suggest that the complement inhibition activity of C1-inh in serum is too low to confer clinical benefit in NMO.
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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.