Evidence map›Paper›PMID 39511877›Full record

ArticleTransfusion2024

A novel small molecule phagocytosis inhibitor, KB-208, ameliorates ITP in mouse models with similar efficacy as IVIG.

Melika Loriamini, Melissa M Lewis-Bakker, Beth Binnington, Lakshmi P Kotra, Donald R Branch

Abstract read
In one paragraph

Article in Transfusion, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
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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

5 authors.

Melika LoriaminiDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Melissa M Lewis-BakkerKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Beth BinningtonCentre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada.
Lakshmi P KotraKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-7071-4637
Donald R BranchDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-8974-2451

Funding

Canadian Blood Services IRGP2024-Branch
6 · The paper itself

Abstract

backgroundThe characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and/or liver engage in the destruction of blood cells that have been opsonized by auto- or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short-term usage along with alternative options. STUDY DESIGN AND

methodsKB-208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB/c, C57BL/6, CD1) were used to determine the efficacy of KB-208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60-day chronic administration of KB-208 by a biochemistry panel, gross necroscopy and histopathology.

resultsKB-208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1 mg/kg in ameliorating ITP, in comparison with IVIG at 1000-2500 mg/kg. KB-208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found.

conclusionKB-208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB-208 for 60 days did not demonstrate in vivo toxicity. These findings indicate that KB-208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology.

Indexed as

Disease Models, AnimalImmunoglobulins, IntravenousPhagocytosisPurpura, Thrombocytopenic, IdiopathicAnimalsFemaleMiceMice, Inbred BALB CMice, Inbred C57BLImmunoglobulins, Intravenousdrug discoveryIVIGphagocytosisphagocytosis inhibitorsmall moleculetransfusion medicine

Identifiers

PMID39511877
PMCPMC11637249

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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.