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Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
Effects of Sphingosine 1-phosphate Modulators on Central Remyelination: A Systematic Review of Animal Models
Harley Vu1, Nelson George1, Junhua Xiao2
1Department of Biomedical, Health and Exercise Sciences, School of Health Sciences, Swinburne University of Technology, Hawthorn, VIC, 3122, Australia.
Cellular and Molecular Neurobiology
|June 10, 2026
Summary
Sphingosine-1-phosphate (S1P) modulators limit myelin loss in demyelinating diseases like multiple sclerosis (MS). However, current therapies show limited efficacy in promoting remyelination, necessitating the development of more effective treatments.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Promoting remyelination is crucial for treating demyelinating diseases like multiple sclerosis (MS).
- Sphingosine-1-phosphate (S1P) is a key therapeutic target in MS, offering immune regulation and neuroprotection.
- The efficacy of S1P modulators in promoting remyelination remains uncertain.
Purpose of the Study:
- To systematically review in vivo studies assessing the efficacy of S1P modulators on remyelination in mammalian demyelination models.
- To evaluate the impact of S1P receptor (S1PR) modulation on myelin loss and oligodendrocyte survival.
- To identify potential therapeutic strategies for improving remyelination in demyelinating diseases.
Main Methods:
- Systematic review of in vivo studies up to July 2025, adhering to PRISMA guidelines.
- Comprehensive database search identifying 24 eligible studies on S1PR modulation in demyelination models.
- Analysis of studies investigating both acute and chronic demyelination, with or without immune components.
Main Results:
- S1P modulation consistently reduced myelin loss and oligodendrocyte depletion across 18 studies.
- However, remyelination outcomes were inconsistent, with 15 studies showing no significant enhancement.
- Fingolimod demonstrated limited remyelination effects, while selective S1PR1/5 modulators showed more promise.
- S1P modulators appear to preserve oligodendrocyte lineage cells rather than drive de novo remyelination.
- Bell-shaped dose-response patterns were observed, emphasizing the importance of dosing and treatment paradigms.
Conclusions:
- Current S1P modulators primarily limit demyelination through immunomodulation and oligodendroglial protection.
- Evidence for enhanced remyelination by S1P modulators is limited.
- Further research is needed to develop more efficacious S1P modulators to improve outcomes in MS and other demyelinating diseases.
