Award Winners at the 8th Annual Martín Villar Haemostasis Awards
Basic Research Prize
The publication "The endothelial protein C receptor enhances hemostasis of FVIIa
administration in hemophilic mice in vivo" by Pavani G, Ivanciu L, Faella A, Marcos-Contreras OA, Margaritis P. (Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA and The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA)
The authors have studied whether endothelial protein C receptor (EPCR) facilitates recombinant activated human factor VII (rhFVIIa) hemostasis using a mouse model of hemophilia. Mouse activated FVII (mFVIIa) is functionally homologous to rhFVIIa, but binds poorly to mouse EPCR (mEPCR). The investigators modified mFVIIa to gain mEPCR binding (mFVIIa-FMR) and discovered that in macrovascular injury models, hemophilic mice administered mFVIIa-FMR showed greater hemostatic activity compared with mFVIIa. This effect was suppressed by blocking mEPCR and was absent in ex vivo whole blood coagulation assays, which indicate a specific mFVIIa-FMR and endothelial mEPCR interaction. These data unmask a novel contribution of EPCR on the action of rhFVIIa administration in hemophilia, thus prompting the rational design of improved and safer rhFVIIa therapeutics.
Clinical Research Prize
The publication "Epitope mapping via selection of anti-FVIII antibody-specific phage presented peptide ligands that mimic the antibody binding sites" by Kahle J, Orlowski A, Stichel D, Becker-Peters K, Kabiri A, Healey JF, Brettschneider K, Naumann A, Scherger AK, Lollar P, Schwabe D, Königs C. (Clinical and Molecular Haemostasis and Immunodeficiency, Department of Paediatrics, Goethe University Hospital, Frankfurt am Main, Germany and Aflac Cancer & Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA)
The authors have developed a novel, general mapping strategy using phage-displayed peptide libraries for the identification of FVIII-specific antibody epitopes in hemophilia A patients with FVIII inhibitors. Precise epitope mapping of anti-FVIII antibodies using antibody-specific peptide ligands can be a useful approach to identify antigenic sites on FVIII. The identification of anti-FVIII antibody-specific peptides via the applied strategy will help to develop new diagnostic tools (e.g. peptide ELISA) for a better understanding of the FVIII immune response. Additionally, peptide ligands may provide further opportunities towards a highly-specific immunotherapy to reduce or even eliminate FVIII inhibitors.