Ravindra C Kodihalli, Mehrdad Ameri, Kevin S Baker, Samantha C Faber, Armando R Irizarry Rovira, Jonathan P Jackson, Leah M Norona, William R Proctor, Jessica M Caverly Rae, Arie Regev, Melanie Z Sakatis, Dominic P Williams, Doris Zane, Payal Rana
{"title":"Contemporary perspective and practical application of glutamate dehydrogenase in nonclinical studies.","authors":"Ravindra C Kodihalli, Mehrdad Ameri, Kevin S Baker, Samantha C Faber, Armando R Irizarry Rovira, Jonathan P Jackson, Leah M Norona, William R Proctor, Jessica M Caverly Rae, Arie Regev, Melanie Z Sakatis, Dominic P Williams, Doris Zane, Payal Rana","doi":"10.1080/17520363.2025.2595911","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9182,"journal":{"name":"Biomarkers in medicine","volume":" ","pages":"1181-1187"},"PeriodicalIF":2.1000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758256/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarkers in medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17520363.2025.2595911","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Biomarkers are physical, functional or biochemical indicators of physiological or disease processes. These key indicators can provide vital information in determining disease prognosis, in predicting of response to therapies, adverse events and drug interactions, and in establishing baseline risk. The explosion of interest in biomarker research is driving the development of new predictive, diagnostic and prognostic products in modern medical practice, and biomarkers are also playing an increasingly important role in the discovery and development of new drugs. For the full utility of biomarkers to be realized, we require greater understanding of disease mechanisms, and the interplay between disease mechanisms, therapeutic interventions and the proposed biomarkers. However, in attempting to evaluate the pros and cons of biomarkers systematically, we are moving into new, challenging territory.
Biomarkers in Medicine (ISSN 1752-0363) is a peer-reviewed, rapid publication journal delivering commentary and analysis on the advances in our understanding of biomarkers and their potential and actual applications in medicine. The journal facilitates translation of our research knowledge into the clinic to increase the effectiveness of medical practice.
As the scientific rationale and regulatory acceptance for biomarkers in medicine and in drug development become more fully established, Biomarkers in Medicine provides the platform for all players in this increasingly vital area to communicate and debate all issues relating to the potential utility and applications.
Each issue includes a diversity of content to provide rounded coverage for the research professional. Articles include Guest Editorials, Interviews, Reviews, Research Articles, Perspectives, Priority Paper Evaluations, Special Reports, Case Reports, Conference Reports and Company Profiles. Review coverage is divided into themed sections according to area of therapeutic utility with some issues including themed sections on an area of topical interest.
Biomarkers in Medicine provides a platform for commentary and debate for all professionals with an interest in the identification of biomarkers, elucidation of their role and formalization and approval of their application in modern medicine. The audience for Biomarkers in Medicine includes academic and industrial researchers, clinicians, pathologists, clinical chemists and regulatory professionals.
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