Characterization of metabolomic biomarkers from a clinical study with coenzyme Q10 in genetically stratified Parkinson’s disease patients
Clinical Neurology; Neurosurgery and Neuroradiology
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
Pathogenic variants in genes linked to monogenic PD, for example, PRKN and PINK1, have been identified as the cause of Parkinson's disease (PD) in 5-10% of cases. These genes code for proteins involved in mitochondrial quality control, suggesting that mitochondrial dysfunction plays a central role in the pathology of (monogenic) PD. Metabolomics describes the quantitative measurement of many metabolites within a sample and the subsequent bioinformatic analysis of the data. Metabolites are involved in various metabolic processes, e.g., epigenetics and the initiation of signaling cascades. A metabolomic biomarker, used to detect a disease or support the monitoring of disease progression, can be a single molecule or a pattern of several molecules. The project's aim was to longitudinally investigate the metabolome of participants in the MitoPD study during the intervention with ubiquinone. MitoPD was a double-blind, randomized, placebo-controlled clinical trial investigating the effects of treating PD with a mitochondrial enhancer (ubiquinone). Idiopathic (IPD) and monogenetic PD patients were divided into subgroups according to the expected degree of mitochondrial dysfunction, and blood plasma and urine samples were taken before, during, and after treatment. These samples were to be analyzed for amino acids, glutathione, biogenic amines, catecholamines, oxidative stress markers such as isoprostanes, nitrosative stress markers, lysophospholipids, bile acids, oxylipins, prostaglandins, endocannabinoids, sphingosine, sphinganine, and fatty acids. This was to i) define a metabolomic signature of the four groups in the biomaterials and ii) investigate the effects of ubiquitin treatment at four-time points in IPD, PRKN, and PINK1-PD patients. We hypothesized that the initial metabolomic signature of untreated patients with impaired mitochondrial function (PRKN and PINK1-PD patients and IPD patients with a strong genetic risk profile) would be altered by treatment with coenzyme Q10. In summary, we wanted to identify metabolic pathways that are altered in certain forms of PD and may be restored by ubiquinone treatment. By analyzing numerous metabolic pathways, we aim to identify metabolites or a metabolomic profile that can be biomarkers for PD in the future.
