Evidence mapPaperPMID 38612432Full record

ArticleInternational journal of molecular sciences2024

Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach.

Morgane Blanot, Ricardo Pedro Casaroli-Marano, Jordi Mondéjar-Medrano, Thaïs Sallén, Esther Ramírez, Cristina Segú-Vergés, Laura Artigas

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 19% 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

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  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

7 authors at 3 institutions in 1 country.

Morgane BlanotAnaxomics Biotech S.L., 08007 Barcelona, Spain.ORCID 0009-0009-2801-5355
Ricardo Pedro Casaroli-MaranoDepartment of Surgery (FMCS), Universitat de Barcelona, 08007 Barcelona, Spain.ORCID 0000-0003-1812-9323
Jordi Mondéjar-MedranoBayer Hispania S.L., 08970 Sant Joan Despí, Spain.
Thaïs SallénBayer Hispania S.L., 08970 Sant Joan Despí, Spain.
Esther RamírezAnaxomics Biotech S.L., 08007 Barcelona, Spain.
Cristina Segú-VergésAnaxomics Biotech S.L., 08007 Barcelona, Spain.ORCID 0000-0002-8215-872X
Laura ArtigasAnaxomics Biotech S.L., 08007 Barcelona, Spain.ORCID 0000-0003-4253-6682
Anaxomics (Spain) · ESHospital Clínic de Barcelona · ESUniversitat Pompeu Fabra · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI's MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes. We also undertook an enrichment analysis to explore the processes modulated by IAI, visualized the effectors' predicted protein activity, and specifically evaluated the role of VEGFR1 pathway inhibition on DME treatment. The models simulated the potential pathophysiology of DME and the likely IAI's MoA by inhibiting VEGFR1 and VEGFR2 signaling. The action of IAI through both signaling pathways modulated the identified pathophysiological processes associated with DME, with the strongest effects in angiogenesis, blood-retinal barrier alteration and permeability, and inflammation. VEGFR1 inhibition was essential to modulate inflammatory protein effectors. Given the role of VEGFR1 signaling on the modulation of inflammatory-related pathways, IAI may offer therapeutic advantages for DME through sustained VEGFR1 pathway inhibition.

Indexed as

Diabetes MellitusDiabetic RetinopathyMacular EdemaReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsComputer SimulationHumansVascular Endothelial Growth Factor AafliberceptReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsVascular Endothelial Growth Factor Aangiogenesisblood–retinal barrier permeabilityinflammationintravitreal aflibercept injectionmachine learningoxidative stresssystems biologyTPMSvascular endothelial growth factor

Identifiers

PMID38612432
PMCPMC11011561
OpenAlexW4393163824

What Socratic holds

Textmetadata
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 Socratic graph.