Collaborative efforts are ongoing to identify valuable biomarkers that can help overcome the hurdles in drug development.
Keratin 18 (K18) (also known as cytokeratin 18), measured by the M65 EpiDeath® ELISA, and caspase-cleaved K18, measured by the M30 Apoptosense® ELISA, are among the select biomarkers that were assessed for their performance and potential among a variety of candidate DILI biomarkers, and further research on K18 to address the need of more sensitive and specific biomarkers in detecting and predicting the outcome of DILI is encouraged.
Peviva products are for research use only.
Safer and Faster Evidence-based Translation and the Predictive Safety Testing Consortium
The SAFE-T consortium consists of a unique partnership between the European Communities and the pharmaceutical industry. Their goal is to address the problems described above and below, withdrawal of drugs in a late stages and patient safety. Their solution is to find new biomarkers with high sensitivity and specificity that detect drug-induced liver, kidney and vascular injury in an earlier stages than what is possible today. To mitigate the issues with standard liver tests, the PSTC, in collaboration with the SAFE-T, is also validating novel liver injury biomarkers. Among the assays of investigations are caspase-cleaved (ccK18) and total keratin 18 (K18), which are studied for application in the regulatory decision making process for use in drug development and as potential drug safety tests.
Detecting potential hepatotoxicity is crucial during drug development and drug safety testing in order to reduce the risk of late drug candidate withdrawal, and pharmaceuticals showing unwanted hepatic side effects entering clinical practice. Today, drug-induced liver injury (DILI) is a leading cause of mortality and morbidity and the cause of more than 50% of all acute liver failure cases. Standard hepatic injury biomarkers show inadequate sensitivity and specificity with limited predictive values.
K18 ELISAs in Drug Development
The M65 EpiDeath® ELISA measures total cell death in epithelial cells of different organs, such as the liver, while the M30 Apoptosense® ELISA measures and provides mechanistic information on liver apoptosis. This is crucial when assessing liver toxicology during drug development and drug safety testing, in order to reduce the risk of unwarranted drug candidate withdrawal, and to identify pharmaceuticals showing unwanted side effects entering clinical practice.
Within both collaborations discussed above, Keratin 18 is considered one of the most promising biomarkers to address the need of more sensitive and specific biomarkers in detecting and predicting the outcome of DILI.
M65 EpiDeath® ELISA measures the concentration of soluble keratin 18 in human plasma, serum and cell culture supernatants. The keratin 18 levels reflect the amount of total cell death, due to apoptosis or necrosis. The M30 Apoptosense® ELISA measures the concentration of soluble caspase-cleaved keratin 18 in human plasma, serum and cell culture supernatants. The caspase-cleaved keratin 18 levels reflect the amount of cell death due to apoptosis of epithelial cells (hepatocytes) only.
- Optimized for identification of subjects with liver damage
- Sandwich ELISA with a 96-well plate in a convenient ready-to-use format
- Can be split up for use at several occasions
- Research Use Only in the US and Canada
K18 Biomarker Features
- Outperforms ALT in specificity when defined as organ of origin
- Highly abundant in liver tissue
- Minimal day-to-day fluctuations in control samples
- Remarkably stable in serum/plasma after sampling
- Relatively short half-life in the circulation for examining effects of a drug
- Provides informative mechanistic information on hepatocyte injury (apoptosis and/or necrosis)