The Cape Chacma baboon is not suitable for evaluating human targeted anti-GPVI agents

Abstract

An effective and safe anti-platelet drug is central to the management of patients with acute coronary syndrome (ACS). Glycoprotein VI (GPVI) is currently regarded as a potential target for novel anti-platelet agents due to its collagen-binding potential. Development of anti-thrombotics is associated with testing in animals. We have previously successfully evaluated anti-platelet drugs in the Cape Chacma baboon (Papio ursinus). However, various anti-GPVI agents did not have an effect on baboons when evaluated in our arterial thrombosis model. To evaluate the suitability of baboons for GPVI studies, we performed collagen-induced platelet aggregation, GPVI quantification and DNA sequencing. Baboon platelets needed double the amount of collagen compared to human platelets to illicit proper aggregation. GPVI quantification was unsuccessful due to non-binding of monoclonal antibodies. Sequencing of the GPVI gene revealed 36 SNPs leading to 14 amino acid changes, as well as a 9 bp deletion causing a 3 amino acid deletion. Several of the amino acid changes were within the ligand binding region of GPVI, causing limited binding of humanized anti-GPVI antibodies to the baboon platelets. Therefore, the baboon was deemed not suitable to evaluate human targeted anti-GPVI agents.

• Animal model
• anti-GPVI Basic

Acknowledgements

The authors would like to acknowledge Dr. Martine Jandrot-Perrus and Prof. Rob Andrew for graciously providing the different anti-GPVI antibodies. We also acknowledge Dr. Daleen Struwig, medical writer, Faculty of Health Sciences, University of the Free State, for assistance with technical and editorial preparation of the manuscript.

Declaration of interest

The authors have no conflict of interest to declare. The research was funded by an NHLS Research Trust grant.

Author contributions

W.J.J.v.R. primarily designed and performed the research, collected, analyzed and interpreted data, performed the statistical analysis, and wrote the manuscript.

P.N.B. assisted with the study design, interpreted data, and critically read the manuscript.

J.P.R. assisted with the study design, interpreted data, and critically read the manuscript.