The DOI matches its Crossref record; 120 of the 120 references it cites were found in a registry or an index.
Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis
Abstract
Until recently, all approved multiple sclerosis (MS) disease treatments were administered parenterally. Oral fingolimod was approved in September 2010 by the US Food and Drug Administration to reduce relapses and disability progression in relapsing forms of MS. In the clinical trials that led to approval, fingolimod reduced not only acute relapses and magnetic resonance imaging lesion activity but also disability progression and brain volume loss, suggesting preservation of tissue. Fingolimod's mechanism of action in MS is not known with certainty. Its active form, fingolimod‐phosphate (fingolimod‐P), is a sphingosine 1‐phosphate receptor (S1PR) modulator that inhibits egress of lymphocytes from lymph nodes and their recirculation, potentially reducing trafficking of pathogenic cells into the central nervous system (CNS). Fingolimod also readily penetrates the CNS, and fingolimod‐P formed in situ may have direct effects on neural cells. Fingolimod potently inhibits the MS animal model, experimental autoimmune encephalomyelitis, but is ineffective in mice with selective deficiency of the S1P 1 S1PR subtype on astrocytes despite normal expression in the immune compartment. These findings suggest that S1PR modulation by fingolimod in both the immune system and CNS, producing a combination of beneficial anti‐inflammatory and possibly neuroprotective/reparative effects, may contribute to its efficacy in MS. In clinical trials, fingolimod was generally safe and well tolerated. Its interaction with S1PRs in a variety of tissues largely accounts for the reported adverse effects, which were seen more frequently with doses 2.5 to 10× the approved 0.5mg dose. Fingolimod's unique mechanism of action distinguishes it from all other currently approved MS therapies. Ann Neurol 2011;69:759–777
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Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
Sallusto, F., Geginat, J., & Lanzavecchia, A. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104702 · Cited by 3,067
A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis
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Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis
Cohen, J. A., Barkhof, F., Comi, G., Hartung, H.-P., Khatri, B. O., Montalban, X., Pelletier, J., Capra, R., Gallo, P., Izquierdo, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907839 · Cited by 2,204
Self-citationSphingosine-1-phosphate: an enigmatic signalling lipid
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Multiple Sclerosis — The Plaque and Its Pathogenesis
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Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
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The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors
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Oral Fingolimod (FTY720) for Relapsing Multiple Sclerosis
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Cited by
Sphingosine-1-Phosphate and Lymphocyte Egress from Lymphoid Organs
Cyster, J. G., & Schwab, S. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075011 · Cited by 815
An update on the biology of sphingosine 1-phosphate receptors
Blaho, V. A., & Hla, T. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r046300 · Cited by 516
Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets
Tschoe, C., Bushnell, C. D., Duncan, P. W., Alexander-Miller, M. A., & Wolfe, S. Q. (2020) · Journal of Stroke · doi:10.5853/jos.2019.02236 · Cited by 490
Multiple Sclerosis: Current and Emerging Disease-Modifying Therapies and Treatment Strategies
Wingerchuk, D. M., & Carter, J. L. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2013.11.002 · Cited by 416
The Role of Astrocytes in Multiple Sclerosis
Ponath, G., Park, C., & Pitt, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00217 · Cited by 359
Metadata
- Authors
- Cohen, J. A., & Chun, J.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2011-04-22
- Volume
- 69
- Issue
- 5
- Pages
- 759-777
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2160209245
- Cited by
- 393
- References
- 120
- FWCI
- 24.61
- Type
- journal article
- Language
- en
- Open access
- closed
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