ArticleMolecular pharmacology2012
S1P(1) receptor modulation with cyclical recovery from lymphopenia ameliorates mouse model of multiple sclerosis.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Effects of Sphingosine 1-phosphate Modulators on Central Remyelination: A Systematic Review of Animal Models.Cellular and molecular neurobiology · 2026Pooled it
- Association of vitamin B1/B6/B12 supplementation with sphingosine-1-phosphate signaling and its receptors in multiple sclerosis patients: relevance to LISPR1 and APOA1-AS.Bioscience reports · 2026Observational
- Selective sphingosine-1-phosphate receptor 1 modulator attenuates blood-brain barrier disruption following traumatic brain injury by inhibiting vesicular transcytosis.Fluids and barriers of the CNS · 2022Article
- Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses.International journal of molecular sciences · 2021Review
- Endothelial S1PCirculation research · 2021Article
- Sphingosine-1-Phosphate Signaling in Ischemic Stroke: From Bench to Bedside and Beyond.Frontiers in cellular neuroscience · 2021Review
- Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.International journal of molecular sciences · 2020Review
- Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Dabigatran Suppresses PAR-1/SphK/S1P Activation of Astrocytes in Experimental Autoimmune Encephalomyelitis Model.Frontiers in molecular neuroscience · 2020Article
- Fingolimod Increases Brain-Derived Neurotrophic Factor Level Secretion from Circulating T Cells of Patients with Multiple Sclerosis.CNS drugs · 2019Article
- Automated production of a sphingosine-1 phosphate receptor 1 (S1P1) PET radiopharmaceutical [Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine · 2019Article
- Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo.Journal of autoimmunity · 2019Article
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- A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue reactivation and hypersensitivity in the lung.Mucosal immunology · 2018Article
- Salutary effects of glibenclamide during the chronic phase of murine experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2017Article
- Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget.Oncotarget · 2017Review
- Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-α signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?Frontiers in pharmacology · 2017Review
- Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Multiple sclerosis (MS) therapies modulate T-cell autoimmunity in the central nervous system (CNS) but may exacerbate latent infections. Fingolimod, a nonselective sphingosine-1-phosphate (S1P) receptor agonist that induces sustained lymphopenia and accumulates in the CNS, represents a new treatment modality for MS. We hypothesized that sustained lymphopenia would not be required for efficacy and that a selective, CNS-penetrant, peripherally short-acting, S1P(1) agonist would show full efficacy in a mouse MS model. Using daily treatment with 10 mg/kg 2-(4-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl amino)ethanol (CYM-5442) at the onset of clinical signs in myelin oligodendrocyte glycoprotein MOG(35-55)- induced experimental allergic encephalomyelitis (EAE), we assessed clinical scores, CNS cellular infiltration, demyelination, and gliosis for 12 days with CYM-5442, vehicle, or fingolimod. CYM-5442 levels in CNS and plasma were determined at experiment termination, and blood lymphopenia was measured 3 and 24 h after the last injection. Plasma levels of cytokines were assayed at the end of the protocol. Changes in S1P(1)-enhanced green fluorescent protein expression on neurons and astrocytes during active EAE and upon CYM-5442 treatment were quantified with flow cytometry and Western blotting by using native-locus enhanced green fluorescent protein-tagged S1P(1) mice. S1P(1) agonism alone reduced pathological features as did fingolimod (maximally lymphopenic throughout), despite full reversal of lymphopenia within each dosing interval. CYM-5442 levels in CNS but not in plasma were sustained. Neuronal and astrocytic S1P(1) expression in EAE was suppressed by CYM-5442 treatment, relative to vehicle, and levels of key cytokines, such as interleukin 17A, were also significantly reduced in drug-treated mice. S1P(1)-selective agonists that induce reversible lymphopenia while persisting in the CNS may be effective MS treatments.
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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.