Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis

Multiple sclerosis (MS) is characterized by primaryinflammation, demyelination, and progressive neurodegeneration.A biochemical MS feature is neuronal mitochondrialdysfunction, compensated by anaerobic metabolism increase,likely aggravating progression of neurodegeneration. Here,we characterized a pragmatic serum profile of compoundsrelated to mitochondrial energy metabolism of potential clinicaluse. Blood samples of 518 well characterized (disability,disease course) MS patients and 167 healthy controls wereanalyzed for serum purines, pyrimidines, creatinine, and lactate.Nine of the 15 compounds assayed, hypoxanthine, xanthine,uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine,and lactate, differed significantly between MSpatientsand controls (p < 0.0001). Using these nine compounds, aunifying Biomarker Score was calculated. Controls and MSpatients had mean Biomarker Scores of 0.4 ± 0.7 and4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Scorewas higher in patients with progressive (6.0 ± 1.8 than withrelapsing remitting disease course (3.6 ± 1.5, p < 0.00001).High association between the Biomarker Score and increase indisability (EDSS) was also observed. Additionally, in 50 patientswho underwent magnetic resonance imaging (MRI),increase in the Biomarker Score correlated to neuroanatomicalalterations. These results, obtained in a large cohort of MSpatients evaluated for serum metabolic compounds connectedto energy metabolism, demonstrated that the Biomarker Scoremight represent a pragmatic, resource saving, easy to obtain,laboratory tool useful to monitor MS patients and predict at anearly stage who will switch from an RR to a progressive diseasecourse. For the first time, it was also clearly shown a linkbetween mitochondrial dysfunction and MRI lesions characteristicof MS.