Drug-Induced Toxicity Biomarkers
Drug-induced toxicity is currently measured by histopathology and blood tests, and the time lag for clinical diagnosis is problematic. Researchers at Compugen have developed a method to discover genetic biomarker signatures to predict the occurrence of drug-induced renal toxicity before it is detected by clinical chemistry, offering an opportunity for early prediction.
Animal studies using rats treated with well-known renal toxins found a subset of four to six genes that were selected as a biomarker signature, indicating nephrotoxicity at day five. The four biomarker combination identified the nephrotoxic drugs following a one- to five-day exposure period, as opposed to a typical 28-day diagnostic timeline, according to the company. In addition, Compugen scientists reported that the biomarker combination successfully predicted the relative levels of toxicity of the compounds tested.
“These results represent the first application of Compugen’s drug-induced toxicity biomarker discovery platform, which incorporates our rat-related predictive transcriptome and proteome,” explained Merav Beiman, Ph.D., head of molecular biology. He added that this database is substantially different in that the modeling of alternative splicing adds a large number of novel proteins and improves the quality of sequence prediction, contributing to the company’s ability to predict disease-related markers.
The platform is designed so that various components can be modified in order to use it for the discovery of novel preclinical biomarkers for other tissue toxicities such as cardio- or hepatotoxicities.