Cited by 131Sphingolipid Metabolism and SignalingMultiple Sclerosis Research StudiesLysosomal Storage Disorders Research

Fingolimod: Lessons Learned and New Opportunities for Treating Multiple Sclerosis and Other Disorders

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Chun, Jerold, Kihara, Yasuyuki, Jonnalagadda, Deepa, Blaho, Victoria A.·2019·Annual Review of Pharmacology and Toxicology

Abstract

Fingolimod (FTY720, Gilenya) was the first US Food and Drug Administration–approved oral therapy for relapsing forms of multiple sclerosis (MS). Research on modified fungal metabolites converged with basic science studies that had identified lysophospholipid (LP) sphingosine 1-phosphate (S1P) receptors, providing mechanistic insights on fingolimod while validating LP receptors as drug targets. Mechanism of action (MOA) studies identified receptor-mediated processes involving the immune system and the central nervous system (CNS). These dual actions represent a more general theme for S1P and likely other LP receptor modulators. Fingolimod's direct CNS activities likely contribute to its efficacy in MS, with particular relevance to treating progressive disease stages and forms that involve neurodegeneration. The evolving understanding of fingolimod's MOA has provided strategies for developing next-generation compounds with superior attributes, suggesting new ways to target S1P as well as other LP receptor modulators for novel therapeutics in the CNS and other organ systems.

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Crossref · 10.1146/annurev-pharmtox-010818-021358

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  • Fingolimod and siponimod are approved for multiple sclerosis.

    “This strategy has been successfully developed with the S1PR1,3–5 agonist fingolimod167 and the S1PR1,5 agonist siponimod168, which are both approved for the therapy of multiple sclerosis.”

    From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [167]

    The “Fingolimod (Gilenya) for Multiple Sclerosis” section states that fingolimod received FDA approval for relapsing MS. The “Next-Generation Lysophospholipid Receptor Modulators and Diseases” section describes siponimod as having entered clinical trials and reports positive phase III results, but does not say it was approved. Page numbers are unavailable in our copy. (LLM, conf=0.90)

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4 retracted

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Research works printed but not linked: 3

  1. [28]Gobley T 1874 Sur la lécithine et la cérébrine. J. Pharm. Chim 19(4): 346– 54
  2. [139]Novartis. 2017 Novartis multiple sclerosis therapy fingolimod granted FDA Breakthrough Therapy designation for pediatric MS Press Release, Dec. 18 https://www.pharma.us.novartis.com/news/mediareleases/novartis-multiple-sclerosis-therapy-fingolimod-granted-fda-breakthrough-therapy
  3. [140]Novartis. 2017 Novartis pivotal data show children and adolescents with relapsing MS had an 82% lower relapse rate with fingolimod vs. interferon beta-1a. Press Release, Oct. 28. https://www.pharma.us.novartis.com/news/media-releases/novartis-pivotal-data-show-children-and-adolescents-relapsing-mshad-82-lower

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Authors
Chun, J., Kihara, Y., Jonnalagadda, D., & Blaho, V. A.
Affiliations
Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
Chun, Jerold
Venue
Annual Review of Pharmacology and Toxicology
Published
2019-01-06
Volume
59
Issue
1
Pages
149-170
ISSN
  • 0362-1642 (ISSN-L)
  • 1545-4304
OpenAlex
W2909092545
Cited by
131
References
165
Citations by year
2026: 19 · 2025: 16 · 2024: 13 · 2023: 18 · 2022: 22 · 2021: 12 · 2020: 18 · 2019: 10 · 2018: 3
FWCI
1.39
Type
journal article
Language
en
Open access
Locations
  • The Annual Review of Pharmacology and Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Defense (#W81XWH-17, W81XWH1710455, W81XWH)
  • American Heart Association (16SDG27020014)
  • National Institutes of Health (W81XWH, NS103940)
  • National Institute of Neurological Disorders and Stroke (R01NS103940, R01NS084398)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
fingolimod, multiple sclerosis, sphingosine-1-phosphate receptor, lysophospholipid receptors, mechanism of action, relapsing multiple sclerosis, neurodegeneration, oral therapy, fungal metabolites, CNS drug targets, drug development
MeSH terms
Fingolimod Hydrochloride, Sphingosine-1-Phosphate Receptors, Animals, Central Nervous System, Humans, Lysophospholipids, Multiple Sclerosis

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