Evidence map›Paper›PMID 32438492›Full record

ArticleCPT: pharmacometrics & systems pharmacology2020

Model-Based Analysis Reveals a Sustained and Dose-Dependent Acceleration of Wound Healing by VEGF-A mRNA (AZD8601).

Joachim Almquist, S Michaela Rikard, Maria Wågberg, Anthony C Bruce, Peter Gennemark, Regina Fritsche-Danielson, Kenneth R Chien, Shayn M Peirce, Kenny Hansson, Anna Lundahl

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. mRNA vaccines in disease prevention and treatment.Signal transduction and targeted therapy · 2023
    Review
  4. Modified mRNA Therapeutics for Heart Diseases.International journal of molecular sciences · 2022
    Review
  5. 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

10 authors at 4 institutions in 3 countries.

Joachim AlmquistDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
S Michaela RikardDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Maria WågbergBioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Anthony C BruceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Peter GennemarkDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Regina Fritsche-DanielsonResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Kenneth R ChienIntegrated Cardiometabolic Center, Karolinska Institute, Huddinge, Sweden.
Shayn M PeirceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Kenny HanssonBioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Anna LundahlDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
AstraZeneca (Sweden) · SEUniversity of Virginia · USFraunhofer Chalmers Research Centre for Industrial Mathematics · SEKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model. Here, we develop population pharmacokinetic and pharmacodynamic models aiming to quantify the effect of AZD8601 injections on the dynamics of wound healing. A dataset of 584 open wound area measurements from 131 mice was integrated from 3 independent studies encompassing different doses, dosing timepoints, and number of doses. Evaluation of several candidate models showed that wound healing acceleration is not likely driven directly by time-dependent VEGF-A concentration. Instead, we found that administration of AZD8601 induced a sustained acceleration of wound healing depending on the accumulated dose, with a dose producing 50% of the maximal effect of 92 µg. Simulations with this model showed that a single dose of 200 µg AZD8601 can reduce the time to reach 50% wound healing by up to 5 days.

Indexed as

AnimalsDiabetes Mellitus, ExperimentalMiceModels, BiologicalRNA, MessengerTime FactorsVascular Endothelial Growth Factor AWound HealingRNA, MessengerVascular Endothelial Growth Factor A

Identifiers

PMID32438492
PMCPMC7376292
OpenAlexW3027381358

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.