Accurate biomarker analysis (partner: Radboudumc)
The Translational Metabolic Laboratory (TML) of the Radboudumc and FELIX Laboratory collaborate to provide an unique analytical service for metabolite (biomarker) identification. We are open to work with interested parties worldwide. With this analytical service we primarily aim to identify novel biomarkers for inborn errors of metabolism that can be incorporated in improved diagnostic protocols.
In the Netherlands, every year more than 800 children are born with a genetic defect affecting their metabolism. Currently, many hundreds of individual metabolic diseases, or inborn errors of metabolism, are recognized. Each differs in clinical symptoms, disease severity and available options for diagnostics, therapy and treatment.
Advertisement of Metakids, a Dutch foundation that fights for a world in which metabolic diseases can be treated and no child has to die from this. They state research is the solution: it makes almost all metabolic diseases treatable within 25 years and offers children quality of life and hope for the future.
Each metabolic disease has a unique chemical fingerprint that can be detected in body fluids of patients. Specialists can use the chemical fingerprint as a biomarker to diagnose the cause of symptoms observed with their patients. Biomarkers can also work in a predictive way to identify disease in the earliest stages, ideally before symptoms and permanent physical harm have manifest.
TML: Unknown molecules detected
The FELIX-TML collaboration brought together two state-of-the-art technologies on the Radboud University campus. The first is the ultra-sensitive instrumentation for 'Next Generation Metabolic Screening', installed at the TML, which enables metabolic profiling of individual patients. Exploiting the ultra-high sensitivity of this technology, a unknown areas of the human metabolome can be uncovered. This ability, however, brings with it an entirely new challenge; approximately 70-80% of these detected molecules have never been identified before and have unknown chemical structures. This question of molecular identification is currently the primary bottleneck in all laboratories using metabolomics.
FELIX: Chemical structures elucidated
The second technology is infrared ion spectroscopy at FELIX, which can provide a structural fingerprint of molecules detected in metabolite screening in patients. This innovative setup is now in use for molecular identification of features detected in untargeted metabolomics experiments. The combination of these two technologies is key to overcome this bottleneck in biomarker discovery; not only can extremely low-abundance metabolites be detected, but their chemical structures can be elucidated.
Unique strategy for metabolite identification
The combination of these two technologies is key to overcome this bottleneck in biomarker discovery; not only can low-abundance metabolites be detected, but their chemical structures can also be elucidated. This unique infrastructure for metabolomics has recently provided our first results illustrating its added value, see:
- Four new biomarkers for pyridoxine-dependent epilepsy identified
- Novel biomarkers for pyridoxine-dependent epilepsy identified using untargeted metabolomics and infrared ion spectroscopy
- Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism