Nonclinical Skeletal Muscle Injury

FEASIBILITY1 SCOPING2 RESEARCH3 SUBMITTED4 QUALIFIED5

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

green European Medicines Agency (EMA)

Overview

Muscle pain is an unfortunate common side effect of treatment in popular classes of drugs, including cholesterol-lowering statins. AST and creatinine kinase activity (CK), traditional measures of drug-induced skeletal muscle injury, lack both specificity and sensitivity. Skeletal troponin I (Tnni1, Tnni2), skeletal troponin T (Tnnt1, Tnnt3), creatinine kinase protein M (Ckm), parvalbumin (Pvalb), myosin light chain 3 (Myl3), fatty acid binding protein 3 (Fabp3), aldolase A (Aldoa), and myoglobin – all measured in serum or plasma – are proposed as more sensitive and specific biomarkers of drug-induced skeletal muscle injury, that additionally may distinguish between injury to fast and slow twitch muscle fiber types in rats. Adoption of these newer biomarkers should allow therapeutics with fewer muscle side-effects to be developed.