Evidence map›Paper›PMID 23518370›Full record

ReviewJournal of the neurological sciences2013

Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy.

Aran Groves, Yasuyuki Kihara, Jerold Chun

Registry-linked trialOpen access · bronzeAbstract readReview
In one paragraph

Review in Journal of the neurological sciences, 2013. 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 174 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 1 pooled it
16.1field-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 mapstarted 2020, after this paper: background citation

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

174 citing papers in PubMed, 1 synthesis or guideline pooled it, 313 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Review
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  15. Review
  16. Article
  17. Choosing initial MS therapy; personal, disease, and medication factors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  18. Review
  19. Article
  20. Review

114 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

3 authors at 1 institution in 1 country.

Aran GrovesThe Scripps Research Institute, Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, 10550 N. Torrey Pines Rd, DNC-118, La Jolla, CA 92037, USA. agroves@scripps.edu
Yasuyuki Kihara
Jerold Chun
Scripps Research Institute · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
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
CELL LINES FOR FINDING DEVELOPMENTAL NEOCORTICAL GENESR29MH051699 · NIMH · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI CHUN, JEROLD · 1994 to 1998
–
NIDA NIH HHS DA019674NIDA NIH HHS R01 DA019674NIGMS NIH HHS T32 GM007198NIGMS NIH HHS T32 GM007752NIMH NIH HHS MH051699NIMH NIH HHS R01 MH051699NINDS NIH HHS NS048478NINDS NIH HHS R01 NS048478
6 · The paper itself

Abstract

Fingolimod is the first oral disease-modifying therapy approved for relapsing forms of multiple sclerosis (MS). Following phosphorylation in vivo, the active agent, fingolimod phosphate (fingolimod-P), acts as a sphingosine 1-phosphate (S1P) receptor modulator, binding with high affinity to four of the five known S1P receptors (S1P1, S1P3, S1P4 and S1P5). The mechanism of action of fingolimod in MS has primarily been considered as immunomodulatory, whereby fingolimod-P modulates S1P1 on lymphocytes, selectively retaining autoreactive lymphocytes in lymph nodes to reduce damaging infiltration into the central nervous system (CNS). However, emerging evidence indicates that fingolimod has direct effects in the CNS in MS. For example, in the MS animal model of experimental autoimmune encephalomyelitis (EAE), fingolimod is highly efficacious in both a prophylactic and therapeutic setting, yet becomes ineffective in animals selectively deficient for S1P1 on astrocytes, despite maintained normal immunologic receptor expression and functions, and S1P-mediated immune activities. Here we review S1P signaling effects relevant to MS in neural cell types expressing S1P receptors, including astrocytes, oligodendrocytes, neurons, microglia and dendritic cells. The direct effects of fingolimod on these CNS cells observed in preclinical studies are discussed in view of the functional consequences of reducing neurodegenerative processes and promoting myelin preservation and repair. The therapeutic implications of S1P modulation in the CNS are considered in terms of the clinical outcomes of MS, such as reducing MS-related brain atrophy, and other CNS disorders. Additionally, we briefly outline other existing and investigational MS therapies that may also have effects in the CNS.

Indexed as

AnimalsCentral Nervous SystemFingolimod HydrochlorideHumansImmunosuppressive AgentsMultiple SclerosisPropylene GlycolsReceptors, LysosphingolipidSphingosineFingolimod HydrochlorideImmunosuppressive AgentsPropylene GlycolsReceptors, LysosphingolipidSphingosine

Identifiers

PMID23518370
PMCPMC3640626
OpenAlexW2170098900

What Socratic 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 Socratic graph.