Application of Metabonomics/Metabolomics for Drug Development
Metabolic profiling of body fluids and tissues by spectroscopic detection of endogenous and drug related metabolites enables the extraction of comprehensive biochemical information, which is of diagnostic and prognostic value. The power of the method relies on three basic properties: (1) there is almost no sample preparation involved; (2) spectroscopic methods, especially NMR, are extremely reproducible;
and (3) the nature of the data reflects actual biological events (physiological phenotype). Metabonomic analyses of body-fluids can be used in early drug development not only for predicting general organ toxicity as described in a preceding section but also for monitoring more specific effects such as phospholipidosis, peroxisome proliferation, changes of the steroidal biosyntheses, and changes of the gut microflora. Apart from monitoring changes of single biomarkers, simultaneous regulations of several metabolites within pathways are investigated. Comparing these changes with a database of metabonomic studies allows identifying studies with similar mechanistic toxicity. It is also demonstrated how metabonomics can be used for identifying new biomarkers, which allow drawing conclusions about mechanistic effects.
Novel and highly relevant biomarkers generated by innovative metabolomics application platform enables pharmaceutical and biotech companies to develop more efficacious and safer compounds as well as reduce time to market. Furthermore, this technology empowers diagnostic companies and hospitals to define and validate novel biomarkers for diagnosis of latent diseases before first symptoms surface. The ultimate objective is to improve the patient’s quality of life through earlier disease detection, therefore, avoiding the need for costly and risky interventions.
Metabolon has used metabolomics to analyze human plasma yielding biomarkers that enables sorting of patients into clinically recognized subsets. These biomarkers are not only diagnostic, but will also provide insights into the underlying pathology and new targets and approaches for drug development.