Evidence map›Paper›PMID 38963161›Full record

ArticleClinical and translational science2024

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Martin O Evans, Darren M Smith, Adrian T Kress, Robert J Nadeau, Daniel J Selig, Diana Caridha, Ratanachat Racharaks, Thomas Langowski, Michael S Madejczyk, Chance Carbaugh and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

15 authors.

Martin O EvansExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0003-2513-8607
Darren M SmithExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0003-4381-9553
Adrian T KressExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Robert J NadeauExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Daniel J SeligExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Diana CaridhaExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Ratanachat RacharaksExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Thomas LangowskiExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Michael S MadejczykExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0002-6000-2599
Chance CarbaughExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0002-9949-691X
David SaundersUniformed Services University School of Medicine, Bethesda, Maryland, USA.
Mark WidderExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Jason De MeeseExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Patricia J LeeExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Jesse P DeLucaExperimental Therapeutics Branch, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen-agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator-led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U-shaped response curve with the greatest effect seen at 0.1 μM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen-agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models.

Indexed as

BenzylaminesCyclamsDisease Models, AnimalHeterocyclic CompoundsReceptors, CXCR4SepsisZebrafishAcinetobacter InfectionsAnimalsAnti-Bacterial AgentsFemaleLipopolysaccharidesMicePseudomonas aeruginosaPseudomonas InfectionsThighAnti-Bacterial AgentsBenzylaminesCyclamsHeterocyclic CompoundsLipopolysaccharidesplerixaforReceptors, CXCR4

Identifiers

PMID38963161
PMCPMC11223064

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Registered trials

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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.