KP-MS Project
Status: Soon to be finished
The Kynurenine Pathway in Multiple Sclerosis (KP-MS) project is a German–Danish collaborative research initiative aimed at deciphering the role of an imbalanced tryptophan metabolism along the kynurenine pathway in Multiple Sclerosis, and how this imbalance can be tackled through endurance exercise. The project explores one of the multiple, still incompletely understood mechanisms by which exercise may act as a potential disease-modifying treatment in Multiple Sclerosis.
The project primarily focuses on data from two Danish randomised controlled trials, complemented by previous trials conducted in Germany, Denmark, and Switzerland. To determine concentrations of kynurenine pathway metabolites, serum samples from study participants were analysed using state-of-the-art targeted metabolomics, employing a high-throughput liquid chromatography–tandem mass spectrometry (LC-MS/MS) pipeline.
RiMS Role in KP-MS
RiMS (Rehabilitation in Multiple Sclerosis) funded a substantial part of the kynurenine pathway metabolomics analyses through the RiMS Grant Programme (RiGra) 2023.
Relevance to MS Rehabilitation
Through the formation of numerous metabolites (kynurenines), the kynurenine pathway plays an important role in immunomodulation, neurotransmission, and neuronal viability. Dysregulation of this pathway is associated with neurotoxic effects and reduced neuronal and glial resilience, while acute and intensive endurance exercise has been shown to beneficially modulate these processes.
The KP-MS project will provide evidence for:
- A holistic characterisation of kynurenine pathway imbalance in Multiple Sclerosis
- The clinical relevance of kynurenine pathway imbalance in Multiple Sclerosis
- The chronic modulation of the kynurenine pathway as a function of exercise modality and intervention duration
Current Status
Metabolomics analyses have been completed. The first manuscript, identifying distinct kynurenine pathway patterns in people with Multiple Sclerosis, has been published in Neurology® Neuroimmunology & Neuroinflammation (https://doi.org/10.1212/NXI.0000000000200461). A second manuscript describing the effects of exercise on kynurenine pathway patterns is currently in preparation.
Related Research Areas
- Application of omics technologies in health and sports research
- Molecular mechanisms of exercise in Multiple Sclerosis