ArticleJournal of neuroinflammation2016
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials.Frontiers in neurology · 2024Pooled it
- Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Trial
- Siponimod: Disentangling disability and relapses in secondary progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2021Trial
- Structural Characterization, Toxicity Assessment and Molecular Modeling of Forced Degradation Products of Siponimod.International journal of molecular sciences · 2026Article
- Evolution of Drug Development Trends in Multiple Sclerosis: Analysis of Mainland China and Global Landscapes From 2004 to 2024.CNS neuroscience & therapeutics · 2026Article
- Effectiveness of Siponimod with Up to 2 Years of Treatment in a Real-World Setting in People with SPMS: Analysis from the Novartis Global Managed Access Program.Degenerative neurological and neuromuscular disease · 2026Article
- Effects of sphingosine-1-phosphate receptor modulators on remyelination in multiple sclerosis: evidence fromFrontiers in immunology · 2026Review
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Design and Synthesis of Novel PET Radiotracers for Imaging Sphingosine-1-Phosphate Receptor 5 (S1PR5) in the Brain.Journal of medicinal chemistry · 2025Article
- Impaired membrane lipids in ischemic stroke: a key player in inflammation and thrombosis.Journal of neuroinflammation · 2025Article
- Investigating the use of cuprizone and lysolecithin to model demyelinationFrontiers in cellular neuroscience · 2025Article
- Microglial Mayhem NLRP3 Inflammasome's Role in Multiple Sclerosis Pathology.CNS neuroscience & therapeutics · 2024Review
- Impact of Siponimod on Clinical and Radiological Parameters of Secondary Progressive Multiple Sclerosis: A Real-World Prospective Study.Journal of clinical neurology (Seoul, Korea) · 2024Article
- The Effect of Donepezil Hydrochloride in the Twitcher Mouse Model of Krabbe Disease.Molecular neurobiology · 2024Article
- Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models.Scientific reports · 2024Article
- Intracerebral haemorrhage in multiple sclerosis: assessing the impact of disease-modifying medications.European journal of medical research · 2024Review
- Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis.Neural regeneration research · 2024Review
- Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways.International journal of molecular sciences · 2024Article
- Investigating the Mitoprotective Effects of S1P Receptor Modulators Ex Vivo Using a Novel Semi-Automated Live Imaging Set-Up.International journal of molecular sciences · 2023Article
- The Benefits and Risks of Switching from Fingolimod to Siponimod for the Treatment of Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.Drugs in R&D · 2023Review
19 more citing papers are in PubMed but not listed here.
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. This drug is currently undergoing clinical trials for the treatment of secondary progressive multiple sclerosis (MS). Here, we investigated the effects of BAF312 on isolated astrocyte and microglia cultures as well as in slice culture models of demyelination.
methodsMouse and human astrocytes were treated with S1PR modulators and changes in the levels of pERK, pAkt, and calcium signalling as well as S1PR1 internalization and cytokine levels was investigated using Western blotting, immunochemistry, ELISA and confocal microscopy. Organotypic slice cultures were prepared from the cerebellum of 10-day-old mice and treated with lysophosphatidylcholine (LPC), psychosine and/or S1PR modulators, and changes in myelination states were measured by fluorescence of myelin basic protein and neurofilament H.
resultsBAF312 treatment of human and mouse astrocytes activated pERK, pAKT and Ca(2+) signalling as well as inducing S1PR1 internalization. Notably, activation of S1PR1 increased pERK and pAKT in mouse astrocytes while both S1PR1 and S1PR3 equally increased pERK and pAKT in human astrocytes, suggesting that the coupling of S1PR1 and S1PR3 to pERK and pAKT differ in mouse and human astrocytes. We also observed that BAF312 moderately attenuated lipopolysaccharide (LPS)- or TNFα/IL17-induced levels of IL6 in both astrocyte and microglia cell cultures. In organotypic slice cultures, BAF312 reduced LPC-induced levels of IL6 and attenuated LPC-mediated demyelination. We have shown previously that the toxic lipid metabolite psychosine induces demyelination in organotypic slice cultures, without altering the levels of cytokines, such as IL6. Importantly, psychosine-induced demyelination was also attenuated by BAF312.
conclusionsOverall, this study suggests that BAF312 can modulate glial cell function and attenuate demyelination, highlighting this drug as a further potential therapy in demyelinating disorders, beyond MS.
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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.