Nonclinical Vascular Injury

FEASIBILITY1 SCOPING2 RESEARCH3 SUBMITTED4 QUALIFIED5

blue U.S. Food & Drug Administration (FDA)

green European Medicines Agency (EMA)

Overview

Drug-induced vascular injury (DIVI) is common in preclinical species such as the rat, dog, or monkey and is classically associated with a class of drugs called PDE inhibitors, including many given safely and effectively to humans for a variety of conditions and diseases. However, observations of histopathology are dissimilar among these species and even more different than histopathology observed in humans. Moreover, compounds known to cause DIVI in preclinical species do not appear to cause vascular injury in humans. PSTC is pursuing biomarkers in rats that are both sensitive and specific to drug-induced injury to the epithelial or smooth muscle cells of the vasculature, and can be demonstrated of mechanistic relevance for humans.

  • First set: VEGF, GRO/CINC-1, TIMP-1, vWGpp, NGAL, TSP-1, smooth muscle alpha actin, calponin, transgelin