title: 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.
authors.affiliation: Department of Hematology and Cell Biology, University of the Free State , Bloemfontein , South Africa .
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Janse van Rensburg
authors.forename: Philip N
authors.initials: PN
authors.lastname: Badenhorst
authors.forename: Jan P
authors.initials: JP
authors.lastname: Roodt
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D023421:Models, Animal; D008969:Molecular Sequence Data; D048549:Papio ursinus; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen
keywords: Animal model; anti-GPVI Basic