ArticleNeural regeneration research2019
The next-generation sphingosine-1 receptor modulator BAF312 (siponimod) improves cortical network functionality in focal autoimmune encephalomyelitis.
Article in Neural regeneration research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Channel Dysfunction as the Basis for Comorbidities in Multiple Sclerosis and Depression.Archiv der Pharmazie · 2026Review
- Insights and challenges on animal models for progressive multiple sclerosis.Journal of neuroinflammation · 2026Review
- 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
- FirstTheranostics · 2023Article
- Bioavailable central nervous system disease-modifying therapies for multiple sclerosis.Frontiers in immunology · 2023Review
- Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2022Article
- Cladribine treatment improves cortical network functionality in a mouse model of autoimmune encephalomyelitis.Journal of neuroinflammation · 2022Article
- Long-term efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis: Analysis of EXPAND core and extension data up to >5 years.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- The Two Sides of Siponimod: Evidence for Brain and Immune Mechanisms in Multiple Sclerosis.CNS drugs · 2022Review
- The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone.The Journal of clinical investigation · 2022Article
- Hippocampal Cytokine Release in Experimental Epileptogenesis-A Longitudinal In Vivo Microdialysis Study.Brain sciences · 2022Article
- Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis.Frontiers in behavioral neuroscience · 2022Article
- Review
- [Disease-modifying treatment of secondary progressive multiple sclerosis].Der Nervenarzt · 2021Review
- Review
- The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations.Frontiers in immunology · 2021Review
- Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation.International journal of molecular sciences · 2020Review
- Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoimmune diseases of the central nervous system (CNS) like multiple sclerosis (MS) are characterized by inflammation and demyelinated lesions in white and grey matter regions. While inflammation is present at all stages of MS, it is more pronounced in the relapsing forms of the disease, whereas progressive MS (PMS) shows significant neuroaxonal damage and grey and white matter atrophy. Hence, disease-modifying treatments beneficial in patients with relapsing MS have limited success in PMS. BAF312 (siponimod) is a novel sphingosine-1-phosphate receptor modulator shown to delay progression in PMS. Besides reducing inflammation by sequestering lymphocytes in lymphoid tissues, BAF312 crosses the blood-brain barrier and binds its receptors on neurons, astrocytes and oligodendrocytes. To evaluate potential direct neuroprotective effects, BAF312 was systemically or locally administered in the CNS of experimental autoimmune encephalomyelitis mice with distinct grey- and white-matter lesions (focal experimental autoimmune encephalomyelitis using an osmotic mini-pump). Ex-vivo flow cytometry revealed that systemic but not local BAF312 administration lowered immune cell infiltration in animals with both grey and white matter lesions. Ex-vivo voltage-sensitive dye imaging of acute brain slices revealed an altered spatio-temporal pattern of activation in the lesioned cortex compared to controls in response to electrical stimulation of incoming white-matter fiber tracts. Here, BAF312 administration showed partial restore of cortical neuronal circuit function. The data suggest that BAF312 exerts a neuroprotective effect after crossing the blood-brain barrier independently of peripheral effects on immune cells. Experiments were carried out in accordance with German and EU animal protection law and approved by local authorities (Landesamt für Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen; 87-51.04.2010.A331) on December 28, 2010.
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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.