Molecular suitability of the chacma baboon in human-targeted Von Willebrand factor directed studies.

Abstract

Von Willebrand factor (VWF) has a central role in primary haemostasis and is a popular pharmaceutical target in the prevention and treatment of disorders such as acute coronary syndrome and thrombotic thrombocytopenic purpura. We have evaluated numerous possible treatments targeting VWF in the chacma baboon. Unfortunately, no data exist regarding the molecular similarity of the chacma baboon and human VWF protein, resulting in limited translatability of results. Sanger sequencing was performed of the functionally vital VWF exon 28. The sequences were then compared to the human reference sequence. The baboon and human VWF amino acid sequences were 99.1% similar, with only 4 radical amino acid changes found. No radical amino acid changes were found within the functionally vital areas of the amino acid sequence. The chacma baboon VWF is similar enough to the human to produce reliable and translatable pre-clinical results with human-targeted anti-VWF agents.