Nonclinical Liver Injury

FEASIBILITY1 SCOPING2 RESEARCH3 SUBMITTED4 QUALIFIED5

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

green European Medicines Agency (EMA)

Overview

The most common traditional biomarkers of drug-induced liver injury, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), have several limitations. In the course of testing a therapeutic for potential to cause liver injury, transaminase increases are commonly observed in the absence of evidence of injury to tissue, and, conversely, sometimes do not increase even when tissue injury is observed. PSTC is pursuing qualification of several biomarkers that improve upon this lack of concordance, as well as biomarkers that may truly predict whether a drug-induced injury will progress to a serious outcome (i.e. liver failure) or whether adaptation may occur.

  • First set: GLDH, MDH, PON-1, PNP
  • Second set: ARG-1, SDH, GST-alpha
  • Third set: miR-122