Factor-VII activating protease (FSAP) is a ubiquitously circulating zymogen plasma serine protease, which is rapidly activated upon tissue injury. FSAPs role in sepsis, trauma, stroke, and acute respiratory distress syndrome suggests that pro-FSAP activation is related to tissue damage and inflammation and may be part of the damage-associated molecular pattern (DAMP) response. Here, active FSAP can cleave and inactivate free histones thereby limit their cytotoxicity. Notably, active FSAP levels are raised in patients, as well as mice after stroke, and a naturally occurring inactive FSAP variant (FSAP-MI) is linked to an increased risk of stroke. Accordingly, a recent preclinical study shows that active FSAP has multiple beneficial effects on stroke progression and outcome – an effect that is not seen with FSAP-MI.
In collaboration with the group of Professor Sandip Kanse at OUS/UiO (Norway), Nextera’s NextCore phage display technology was recently applied to identify a novel peptide specifically and rapidly transforming pro-FSAP into its active form in human plasma.
Read the paper here: https://pubs.acs.org/doi/10.1021/acschembio.2c00538
This novel peptide represents both a unique new tool to establish the molecular details of FSAP zymogen activation and the biological role of FSAP, as well as being a starting point devoid of histone toxic effects to therapeutically target endogenous blood pro-FSAP to e.g improve outcome in stroke.