epilepsy awareness
epilepsy awareness

Novel NMR technique demonstrates biomarkers of rare epilepsy disease

Researchers from the Institute for Molecules and Materials (IMM) at Radboud University have demonstrated that non-hydrogenative parahydrogen induced hyperpolarization (nhPHIP),a special technique for enhancing NMR sensitivity, could successfully be employed for detecting biomarkers of the rare metabolic disease pyridoxine-dependent epilepsy (PDE). Due to the enhanced sensitivity, the method makes it possible to detect signals that remain hidden when using standard NMR techniques. The results highlight a new application of nhPHIP-NMR and mark an important step towards better analysis of complex biological mixtures.

Making NMR more sensitive

NMR spectroscopy is a common tool to study molecules, but it is not always sensitive enough. nhPHIP is a variant of NMR that boosts the signal, making small details easier to detect. Not many groups use this technique yet, because there are few known applications. “With this project, we wanted to show that the technique is reaching maturity”, PhD researcher Thom Posthumus says. 

Unique biomarkers

In collaboration with colleagues from IMM, the Boltje Lab, HFML-FELIX, and Radboud University Medical Center, the team lead by Marco Tessari (MRRC) focused on PDE, a rare disease characterized by unique biomarkers. This rare disease is marked by unique molecules, biomarkers that were previously discovered in Nijmegen. The team showed that nhPHIP could clearly detect these biomarkers in urine of PDE patients, and not in urine of healthy subjects. By analysing the data with metabolomics, a method to deal with large sets of biological data, they were able to inequivocably distinguish PDE patients from healthy controls.

Clearer results than standard methods

To test the strength of nhPHIP, the researchers performed the same comparison between urine samples of PDE patients and healthy subjects using standard NMR. In the standard NMR dataset, no clear separation could be observed between the two groups, and the results appeared inconsistent. The findings highlight PHIP as a promising technique for studying complex mixtures, where regular methods fall short. “With this new application, we show that nhPHIP is an excellent auxiliary tool for metabolomics”, Posthumus says. The study demonstrates that nhPHIP has great potential for analysing complex mixtures. The findings have recently been published in the Journal of the American Chemical Society. 

Magnetic Resonance Research Center

Thom Posthumus is working as PhD researcher in the Magnetic Resonance Research Center (MRRC). The MRRC is a research facility and focuses on the development of novel methods to optimize the sensitivity and information content of NMR spectra and apply these methodologies to gain deeper insight into the structure and dynamics of molecules and materials. Applications are particularly geared at unravelling complex mixtures in the liquid state, whereas in the solid state, we investigate phase composition, chemical structure, conformation and dynamics in relation to the functional behavior of energy materials (batteries and solar cells), catalysts and polymers.

Semi-Targeted Nuclear Magnetic Resonance Metabolomics via Parahydrogen-Induced Hyperpolarization for Enhanced Sensitivity to Metabolic Composition
Literature reference

Semi-Targeted Nuclear Magnetic Resonance Metabolomics via Parahydrogen-Induced Hyperpolarization for Enhanced Sensitivity to Metabolic Composition
Thom B. Posthumus, Udo F. H. Engelke, Ruud L. E. G. Aspers, Jona Merx, Thomas J. Boltje, Jonathan Martens, Ron A. Wevers, Martin C. Feiters, Floris P. J. T. Rutjes, and Marco Tessari
Journal of the American Chemical Society (2025)
Semi-Targeted Nuclear Magnetic Resonance Metabolomics via Parahydrogen-Induced Hyperpolarization for Enhanced Sensitivity to Metabolic Composition | Journal of the American Chemical Society