Evidence map›Paper›PMID 20061941›Full record

ReviewClinical neuropharmacology

Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis.

Jerold Chun, Hans-Peter Hartung

Registry-linked trialOpen access · greenAbstract readReview
In one paragraph

Review in Clinical neuropharmacology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04088630 (Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage), which is not on this map. Cited by 411 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
411citing papers in PubMed, 5 pooled it
17.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04088630 early_phase1completednot on this map

Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage

TypeinterventionalSponsorWake Forest University Health SciencesRan2020 to 2024Enrolled28ConditionsIntracerebral Hemorrhage, Cerebral Edema, Stroke Hemorrhagic, Intracerebral Hemorrhage, HypertensiveArmsFingolimod, Placebo, Open-label Fingolimod
3 · Its place in the literature

Who cites it

411 citing papers in PubMed, 5 syntheses or guidelines pooled it, 786 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Siponimod for multiple sclerosis.The Cochrane database of systematic reviews · 2021
    Pooled it
  4. Pooled it
  5. Pooled it
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  11. Review
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351 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Jerold ChunDepartment of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, CA, USA. jchun@scripps.edu
Hans-Peter Hartung
Heinrich Heine University Düsseldorf · DEScripps Research Institute · US

Funding

RECEPTOR-MEDIATED LPA SIGNALING IN CORTICAL DEVELOPMENTR01MH051699 · NIMH · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI CHUN, JEROLD · 2001 to 2009
$3.3M
Lysophospholipids roles for Schwann cell &myelinationR01NS048478 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI CHUN, JEROLD · 2004 to 2008
$2.4M
Receptor-mediated S1P signaling in the embryonic brainR01DA019674 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI CHUN, JEROLD · 2006 to 2010
$1.9M
Interactions of LPA and prostaglandins in implantationR01HD050685 · NICHD · SCRIPPS RESEARCH INSTITUTE, THE · PI CHUN, JEROLD · 2006 to 2010
$1.9M
Targeting S1P receptors to prevent hearing lossR21DC009505 · NIDCD · SCRIPPS RESEARCH INSTITUTE, THE · PI CHUN, JEROLD · 2009 to 2010
$520k
NICHD NIH HHS R01 HD050685NIDA NIH HHS R01 DA019674NIDCD NIH HHS R21 DC009505NIMH NIH HHS R01 MH051699NINDS NIH HHS R01 NS048478
6 · The paper itself

Abstract

Fingolimod (FTY720) is a first-in-class orally bioavailable compound that has shown efficacy in advanced clinical trials for the treatment of multiple sclerosis (MS). In vivo, fingolimod is phosphorylated to form fingolimod-phosphate, which resembles naturally occurring sphingosine 1-phosphate (S1P), an extracellular lipid mediator whose major effects are mediated by cognate G protein-coupled receptors. There are at least 5 S1P receptor subtypes, known as S1P subtypes 1-5 (S1P1-5), 4 of which bind fingolimod-phosphate. These receptors are expressed on a wide range of cells that are involved in many biological processes relevant to MS. S1P1 plays a key role in the immune system, regulating lymphocyte egress from lymphoid tissues into the circulation. Fingolimod-phosphate initially activates lymphocyte S1P1 via high-affinity receptor binding yet subsequently induces S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system (CNS). S1P receptors are also expressed by many CNS cell types and have been shown to influence cell proliferation, morphology, and migration. Fingolimod crosses the blood-brain barrier and may therefore have direct CNS effects, distinguishing it from immunologically targeted MS therapies. Prophylactic administration of fingolimod to animals with experimental autoimmune encephalitis (EAE), a model of MS, completely prevents development of EAE features, whereas therapeutic administration significantly reduces clinical severity of EAE. Therapeutic efficacy observed in animal studies has been substantiated in phase 2 and 3 trials involving patients with relapsing or relapsing-remitting MS.

Indexed as

Administration, OralAnimalsCentral Nervous SystemEncephalomyelitis, Autoimmune, ExperimentalFingolimod HydrochlorideHumansImmune SystemImmunosuppressive AgentsLymphocytesModels, ImmunologicalMultiple SclerosisNeurogliaNeuronsPropylene GlycolsReceptors, LysosphingolipidSphingosineFingolimod HydrochlorideImmunosuppressive AgentsPropylene GlycolsReceptors, LysosphingolipidSphingosine

Identifiers

PMID20061941
PMCPMC2859693
OpenAlexW2153518194

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.