ArticleJournal of neuroinflammation2016
Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 89 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Clinical Relevance of miR-142-3p as Potential Biomarker of Synaptopathy in Multiple Sclerosis
Interventional Not Pharmacological Study to Investigate the Role of ADA in Multiple Sclerosis PatientsTreated With an Immune-Reconstitution Therapy (2-CdA)
Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 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
- Siponimod for multiple sclerosis.The Cochrane database of systematic reviews · 2021Pooled 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
- Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland.PharmacoEconomics · 2021Trial
- Therapeutic reactivation of hippocampal progenitors reverse cognition decline in mice with progressive brain demyelination.Stem cell reports · 2026Article
- Insights and challenges on animal models for progressive multiple sclerosis.Journal of neuroinflammation · 2026Review
- Siponimod for relapsing-remitting multiple sclerosis: a single-center, real-world cohort study in China.BMC neurology · 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
- Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.Gut microbes · 2025Review
- High efficacy therapy to prevent the formation of meningeal tertiary lymphoid organs after CXCL13 index screening in early multiple sclerosis.Frontiers in neuroscience · 2025Article
- Microglial Mayhem NLRP3 Inflammasome's Role in Multiple Sclerosis Pathology.CNS neuroscience & therapeutics · 2024Review
- Towards Treating Multiple Sclerosis Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- ACKR3 Antagonism Enhances the Repair of Demyelinated Lesions Through Both Immunomodulatory and Remyelinating Effects.Neurochemical research · 2024Article
- Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models.Scientific reports · 2024Article
- Contribution of microglia/macrophage to the pathogenesis of TMEV infection in the central nervous system.Frontiers in microbiology · 2024Review
- Re-emergence of T lymphocyte-mediated synaptopathy in progressive multiple sclerosis.Frontiers in immunology · 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
- Anti-inflammatory Effects of Siponimod in a Mouse Model of Excitotoxicity-Induced Retinal Injury.Molecular neurobiology · 2023Article
29 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
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundData from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE.
methodsMinipumps allowing continuous intracerebroventricular (icv) infusion of siponimod for 4 weeks were implanted into C57BL/6 mice subjected to MOG35-55-induced EAE. Electrophysiology, immunohistochemistry, western blot, qPCR experiments, and peripheral lymphocyte counts were performed. In addition, the effect of siponimod on activated microglia was assessed in vitro to confirm the direct effect of the drug on CNS-resident immune cells.
resultsSiponimod administration (0.45 μg/day) induced a significant beneficial effect on EAE clinical scores with minimal effect on peripheral lymphocyte counts. Siponimod rescued defective GABAergic transmission in the striatum of EAE, without correcting the EAE-induced alterations of glutamatergic transmission. We observed a significant attenuation of astrogliosis and microgliosis together with reduced lymphocyte infiltration in the striatum of EAE mice treated with siponimod. Interestingly, siponimod reduced the release of IL-6 and RANTES from activated microglial cells in vitro, which might explain the reduced lymphocyte infiltration. Furthermore, the loss of parvalbumin-positive (PV+) GABAergic interneurons typical of EAE brains was rescued by siponimod treatment, providing a plausible explanation of the selective effects of this drug on inhibitory synaptic transmission.
conclusionsAltogether, our results show that siponimod has neuroprotective effects in the CNS of EAE mice, which are likely independent of its peripheral immune effect, suggesting that this drug could be effective in limiting neurodegenerative pathological processes in MS.
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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.