- Bundesministerium für Bildung und Forschung (BMBF)
- Projektträger Jülich
For the detection of biomarkers, specific tests are often required for different model organisms in order to detect effects or side effects of biologically active substances (drug candidates). An antibody-based method has been combined with mass spectrometry to accelerate biomarker test development and subsequent measurement. The innovative step for this analytical procedure lies in the design of the assay. Antibodies are developed that are directed against an epitope of the target analyte that is present in all relevant model organisms and in humans. This makes it easier to perform comparisons in humans and animals.
Protein biomarkers are key factors in drug development and are used in preclinical and clinical phases for toxicity testing, efficacy demonstration and patient stratification. To date, a number of proteins have been identified as biomarkers indicating drug-induced organ damage in the kidney. Corresponding protein biomarkers for the specific detection of liver and cardiovascular damage are currently being validated in clinical trials by publicly funded consortia of pharmaceutical companies and academic working groups.
A significant time and economic limitation in the validation of protein biomarkers and the early phase of drug development lies in the complex translation of animal experimental results to humans. In the preclinical phase, drug candidates are tested for efficacy and toxicity in various model organisms. Due to the genetic differences, however, there is still no method available for detecting protein biomarkers in an assay across species. Until now, conventional detection methods such as sandwich immunoassays have had to be developed and validated individually for each species in time-consuming and cost-intensive processes.
With the Cross Species Immunoassay Technology (XIM) we are able to determine and quantify protein biomarkers in biological samples across species in all pharma-relevant animal models and humans. XIM technology is based on specific antibodies that bind to short peptide motifs selected with proprietary software. These peptide motifs can be used to measure protein biomarkers in all animal models relevant for drug development and in humans. After initial immune enrichment, the biomarkers are uniquely detected and quantified in a mass spectrometer using an internal isotope control.
