Evidence map›Paper›PMID 37111598›Full record

ArticlePharmaceutics2023

Platelet Activation by Antisense Oligonucleotides (ASOs) in the Göttingen Minipig, including an Evaluation of Glycoprotein VI (GPVI) and Platelet Factor 4 (PF4) Ontogeny.

Allan Valenzuela, Miriam Ayuso, Laura Buyssens, Chloé Bars, Chris Van Ginneken, Yann Tessier, Steven Van Cruchten

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
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 2 institutions in 2 countries.

Allan ValenzuelaComparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical Sciences, Biomedical, and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.ORCID 0000-0002-6695-1779
Miriam AyusoComparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical Sciences, Biomedical, and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.ORCID 0000-0001-6045-394X
Laura BuyssensComparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical Sciences, Biomedical, and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.ORCID 0000-0002-2167-4173
Chloé BarsComparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical Sciences, Biomedical, and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.ORCID 0000-0002-9231-4458
Chris Van GinnekenComparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical Sciences, Biomedical, and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.ORCID 0000-0002-1622-9120
Yann TessierRoche Pharmaceutical Research and Early Development, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Steven Van CruchtenComparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical Sciences, Biomedical, and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.ORCID 0000-0002-3144-1840
University of Antwerp · BERoche (Switzerland) · CH

Funding

University of Antwerp 42354
6 · The paper itself

Abstract

Antisense oligonucleotide (ASO) is a therapeutic modality that enables selective modulation of undruggable protein targets. However, dose- and sequence-dependent platelet count reductions have been reported in nonclinical studies and clinical trials. The adult Göttingen minipig is an acknowledged nonclinical model for ASO safety testing, and the juvenile Göttingen minipig has been recently proposed for the safety testing of pediatric medicines. This study assessed the effects of various ASO sequences and modifications on Göttingen minipig platelets using in vitro platelet activation and aggregometry assays. The underlying mechanism was investigated further to characterize this animal model for ASO safety testing. In addition, the protein abundance of glycoprotein VI (GPVI) and platelet factor 4 (PF4) was investigated in the adult and juvenile minipigs. Our data on direct platelet activation and aggregation by ASOs in adult minipigs are remarkably comparable to human data. Additionally, PS ASOs bind to platelet collagen receptor GPVI and directly activate minipig platelets in vitro, mirroring the findings in human blood samples. This further corroborates the use of the Göttingen minipig for ASO safety testing. Moreover, the differential abundance of GPVI and PF4 in minipigs provides insight into the influence of ontogeny in potential ASO-induced thrombocytopenia in pediatric patients.

Indexed as

antisense oligonucleotide (ASO)glycoprotein VI (GPVI)Göttingen minipigontogenyplatelet factor 4 (PF4)safety testingthrombocytopenia

Identifiers

PMID37111598
PMCPMC10143489
OpenAlexW4362470109

What OpenQuestion 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 OpenQuestion graph.