Project Towards novel translational safety biomarkers for adverse drug toxicity

Objectives

Adverse drug reactions (ADRs) related to hepatotoxicity, blood dyscrasias and drug hypersensitivity are responsible for the top 3 of drug withdrawals due to toxicity. Many attrition-linked ADRs involve the low-level formation of reactive intermediates. In addition, the immune system plays a central role in the exacerbation of such toxic responses. Today, no adequate translational strategies are available to predict drug safety.

The objective of this study is to discover appropriate biomarkers and to determine their predictive potential by proteomic profiling of urine samples from selected patients with ADRs as a result of drug exposure. The ultimate goal is to establish a library of profiles of proteomic ADR patterns that can be used to compare patterns elicited by a unknown compound to predict its potential toxicity. In addition, a diagnostic tool could be developed to monitor patients that use certain drugs, for the onset of ADRs.

Protein profiles of urine samples of selected patients and healthy controls are determined and compared by using a proteomics technique called MALDI-TOF MS. Besides human urine samples, also animal urine and tissue samples are collected and analyzed to correlate the protein profiles to the pathology of the ADR. LC-MS/MS techniques can be used for protein identification and biomarker verification on selected urine samples.