Assays - Peptide FX-06

The fibrin-derived peptide Bβ15-42 is cardioprotective in a pig model of myocardial ischemia-reperfusion injury

Author: J.P. Roesner, P. Petzelbauer, A. Koch, J. Mersmann, P.A. Zacharowski, O. Boehm, S. Reingruber, W. Pasteiner, D.G. Mascher, M. Wolzt, C. Barthuber, G.E.F. Nöldge-Schomburg, T.W.L. Scheeren, K. Zacharowski
Publisher: Crit Care Med 2007, 35, 1730 - 1735


Objective: The fibrin-derived peptide Bβ15-42 has been shown to reduce infarct size in rodent models of ischemia-reperfusion injury. To increase its potential for translation into the clinic, we studied the effects of Bβ15-42 in pigs, whose coronary anatomy is similar to that of humans. In addition, we evaluated the pharmacokinetics and safety of Bβ15-42 in several species, including humans.

Design: Animal study and phase I trial.
Setting: University hospital and contract research laboratories.
Subjects: Pigs / healthy volunteers.

Interventions: Male farm-bred Landrace pigs were subjected to 1 hr of left anterior descending coronary artery occlusion followed by 3 hrs of reperfusion. At the time of reperfusion, Bβ15-42 (2.4 mg/kg, n = 6) or random peptide (control; 2.4 mg/kg, n = 6) was administered as an intravenous bolus. As a positive control, pigs were subjected to ischemic preconditioning (n = 6). Cardiac damage and hemodynamics were recorded. Biodistribution and pharmacokinetics of Bβ15-42 were determined in rats and dogs. In a phase I trial involving 30 male healthy volunteers, pharmacokinetics and safety were tested in a randomized, double-blinded, placebo-controlled, parallel-group, single ascending dose study.

Measurement and Main Results: Bβ15-42 and ischemic preconditioning significantly reduced myocardial infarct size and troponin I levels. Bβ15-42 also reduces interleukin-6 levels, underlining its anti-inflammatory properties. Furthermore, in humans, the pharmacokinetics of the peptide Bβ15-42 were comparable to those of animals, and no serious adverse effects were observed.

Conclusions: Bβ15-42 elicits cardioprotection in pigs and is clinically safe in phase I testing of humans. This study confirms the new concept of a pathogenic role of fibrin derivatives in myocardial reperfusion injury, which can be inhibited by peptide Bβ15-42