Key result
Cape Chacma baboons fail as models for human anti-GPVI agents because genetic differences prevent antibody binding.
Why the study?
The suitability of the Cape Chacma baboon for evaluating human targeted anti-GPVI agents was uncertain due to lack of effect of these agents in prior arterial thrombosis models.
The Cape Chacma baboon is not a suitable animal model for evaluating human-targeted anti-GPVI anti-platelet agents due to genetic differences in the GPVI ligand binding region.
Answers are grounded in this paper and cite their sources.
Cape Chacma baboons unsuitable for human anti-GPVI evaluation; leaves open identification of valid preclinical models.
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.
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Rensburg et al. (2014) studied Acute coronary syndrome (animal model evaluation). Human targeted anti-GPVI agents vs. Human platelets was evaluated on Suitability of baboons for GPVI studies (collagen-induced platelet aggregation, GPVI quantification, and DNA sequencing). The Cape Chacma baboon is not a suitable model for evaluating human targeted anti-GPVI agents due to genetic differences in the GPVI ligand binding region preventing antibody binding.
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