Evidence map›Paper›PMID 31736980›Full record

ArticleFrontiers in immunology2019

OLT1177 (Dapansutrile), a Selective NLRP3 Inflammasome Inhibitor, Ameliorates Experimental Autoimmune Encephalomyelitis Pathogenesis.

Alba Sánchez-Fernández, Damaris B Skouras, Charles A Dinarello, Rubèn López-Vales

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
3.6field-weighted citation impact, top 6% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 154 citations in OpenAlex.

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28 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

4 authors at 3 institutions in 3 countries.

Alba Sánchez-FernándezInstitut de Neurociencies and Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, Bellaterra, Spain.
Damaris B SkourasOlatec Therapeutics LLC, NewYork, NY, United States.
Charles A DinarelloDepartment of Medicine, University of Colorado Denver, Aurora, CO, United States.
Rubèn López-ValesInstitut de Neurociencies and Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, Bellaterra, Spain.
Universitat Autònoma de Barcelona · ESOlatec (United States) · USUniversity of Colorado Denver · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

IL-1β and IL-18 are pro-inflammatory cytokines that are linked to inflammation. Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the maturation and secretion of IL-1β and IL-18 and, thus, plays a key role in the pathogenesis of many inflammatory conditions, including multiple sclerosis (MS). OLT1177™ (Dapansutrile) is a newly developed drug that is safe in humans and inhibits specifically the NLRP3 inflammasome. In the present study, we investigated whether OLT1177 exerts therapeutic effects in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We found that EAE mice fed an OLT1177-enriched diet prophylactically were significantly protected against functional deficits and demyelination in the spinal cord. We also demonstrated that prophylactic oral administration of OLT1177 led to marked reduction (~2- to 3-fold) in the protein levels of IL-1β and IL-18, as well as, IL-6 and TNFα, in the spinal cord of EAE mice. Moreover, prophylactic oral administration of OLT1177 significantly attenuated the infiltration of CD4 T cells and macrophages in the spinal cord. We also demonstrated that oral administration of OLT1177, starting at disease onset, resulted in significant amelioration of the clinical signs of EAE. Overall, these first data suggest that OLT1177 could have clinical benefit for the treatment of MS in humans.

Indexed as

Administration, OralAnimalsAnti-Inflammatory AgentsCD4-Positive T-LymphocytesCognitive DysfunctionEncephalomyelitis, Autoimmune, ExperimentalFemaleInflammasomesMacrophagesMice, Inbred C57BLNitrilesNLR Family, Pyrin Domain-Containing 3 ProteinSpinal CordSulfonesAnti-Inflammatory AgentsdapansutrileInflammasomesNitrilesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseSulfonescytokinesexperimental autoimmune encephalomyelitisinflammationNLRP3OLT1177

Identifiers

PMID31736980
PMCPMC6839275
OpenAlexW2982167758

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.