Contemporary perspective and practical application of glutamate dehydrogenase in nonclinical studies.

The use of biomarkers in nonclinical species has gained significant attention for improving predictive accuracy in toxicological studies and early disease detection. This article focuses on glutamate dehydrogenase (GLDH), a mitochondrial enzyme currently under regulatory review for qualification as a clinical biomarker to detect hepatocellular injury in patients with elevated serum transaminases due to muscle injury. GLDH has shown effectiveness in evaluating liver injury, particularly in rodents and non-human primates. This opinion paper outlines the potential of GLDH as a biomarker for monitoring drug-induced liver injury (DILI), drawing on the expertise of authors from the IQ DILI Initiative. It highlights industry consensus on GLDH use in nonclinical studies and its relevance in toxicology and drug development. The advantages and challenges of GLDH are discussed, including its interpretation as a mechanistic biomarker with translational relevance. Recent advancements in GLDH research in nonclinical species with different disease backgrounds and therapeutic modalities are explored. The integration of GLDH with other biomarkers to enhance the overall assessment of nonclinical species is reviewed. Our collective consensus opinion on GLDH is that it may offer an additional benefit over traditional biomarkers for hepatotoxicity, particularly when test articles cause increased serum transaminases due to concurrent muscle injury.