siponimod and Demyelinating-Diseases

siponimod has been researched along with Demyelinating-Diseases* in 3 studies

Reviews

1 review(s) available for siponimod and Demyelinating-Diseases

ArticleYear
Multiple sclerosis.
    Nature reviews. Disease primers, 2018, 11-08, Volume: 4, Issue:1

    Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop. A minority of patients have a progressive disease course from the onset. The pathological hallmark of MS is the formation of demyelinating lesions in the brain and spinal cord, which can be associated with neuro-axonal damage. Focal lesions are thought to be caused by the infiltration of immune cells, including T cells, B cells and myeloid cells, into the central nervous system parenchyma, with associated injury. MS is associated with a substantial burden on society owing to the high cost of the available treatments and poorer employment prospects and job retention for patients and their caregivers.

    Topics: Azetidines; Benzyl Compounds; Demyelinating Diseases; Humans; Indans; Magnetic Resonance Imaging; Multiple Sclerosis; Oxadiazoles; Risk Factors; Thiazoles; Tomography, X-Ray Computed

2018

Other Studies

2 other study(ies) available for siponimod and Demyelinating-Diseases

ArticleYear
Effect of Siponimod on Brain and Spinal Cord Imaging Markers of Neurodegeneration in the Theiler's Murine Encephalomyelitis Virus Model of Demyelination.
    International journal of molecular sciences, 2023, Aug-20, Volume: 24, Issue:16

    Siponimod (Sp) is a Sphingosine 1-phosphate (S1P) receptor modulator, and it suppresses S1P- mediated autoimmune lymphocyte transport and inflammation. Theiler's murine encephalomyelitis virus (TMEV) infection mouse model of multiple sclerosis (MS) exhibits inflammation-driven acute and chronic phases, spinal cord lesions, brain and spinal cord atrophy, and white matter injury. The objective of the study was to investigate whether Sp treatment could attenuate inflammation-induced pathology in the TMEV model by inhibiting microglial activation and preventing the atrophy of central nervous tissue associated with neurodegeneration. Clinical disability score (CDS), body weight (BW), and rotarod retention time measures were used to assess Sp's impact on neurodegeneration and disease progression in 4 study groups of 102 animals, including 44 Sp-treated (SpT), 44 vehicle-treated, 6 saline-injected, and 8 age-matched healthy controls (HC). Next, 58 (22 SpT, 22 vehicle, 6 saline injected, and 8 HC) out of the 102 animals were further evaluated to assess the effect of Sp on brain region-specific and spinal cord volume changes, as well as microglial activation. Sp increased CDS and decreased BW and rotarod retention time in TMEV mice, but did not significantly affect most brain region volumes, except for lateral ventricle volume. Sp suppressed ventricular enlargement, suggesting reduced TMEV-induced inflammation in LV. No significant differences in spine volume changes were observed between Sp- and vehicle-treated animals, but there were differences between HC and TMEV groups, indicating TMEV-induced inflammation contributed to increased spine volume. Spine histology revealed no significant microglial density differences between groups in gray matter, but HC animals had higher type 1 morphology and lower type 2 morphology percentages in gray and white matter regions. This suggests that Sp did not significantly affect microglial density but may have modulated neuroinflammation in the spinal cord. Sp may have some effects on neuroinflammation and ventricular enlargement. However, it did not demonstrate a significant impact on neurodegeneration, spinal volume, or lesion volume in the TMEV mouse model. Further investigation is required to fully understand Sp's effect on microglial activation and its relevance to the pathophysiology of MS. The differences between the current study and previous research using other MS models, such as EAE, highlight the differences in path

    Topics: Animals; Atrophy; Brain; Demyelinating Diseases; Disease Models, Animal; Mice; Neuroinflammatory Diseases; Spinal Cord; Theilovirus

2023
The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.
    Journal of neuroinflammation, 2016, Feb-08, Volume: 13

    BAF312 (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.. Mouse 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.. BAF312 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.. Overall, 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.

    Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Astrocytes; Azetidines; Benzyl Compounds; beta-Alanine; Calcium Signaling; Cerebellum; Demyelinating Diseases; eIF-2 Kinase; Humans; Immunosuppressive Agents; In Vitro Techniques; Indans; Interleukin-6; Lysophosphatidylcholines; Mice; Myelin Basic Protein; Organ Culture Techniques; Oxadiazoles; Protein Transport; Receptors, Lysosphingolipid; Thiophenes; Time Factors

2016
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