Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis.
Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed 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 MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Giacomo
G
Lazzarino
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Angela M
AM
Amorini
Department of Neurology, VU Medical Centre, Amsterdam, The Netherlands.|Moorfields Eye Hospital, City Road, London, UK.|UCL Institute of Neurology, Queen Square, London, UK.
Axel
A
Petzold
Department of Neurosciences, S Camillo-Forlanini Hospital, Rome, Italy.
Claudio
C
Gasperini
Department of Neurosciences, S Camillo-Forlanini Hospital, Rome, Italy.|Department of Neurology and Psychiatry, University of Rome "La Sapienza", Rome, Italy.
Serena
S
Ruggieri
Department of Neurosciences, S Camillo-Forlanini Hospital, Rome, Italy.
Maria Esmeralda
ME
Quartuccio
Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Bldg. 2, III Floor, Viale A. Doria 6, 95125, Catania, Italy. lazzarig@unict.it.
Giuseppe
http://orcid.org/0000-0002-5917-7279
G
Lazzarino
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Enrico
E
Di Stasio
Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Rome, Italy.
Barbara
B
Tavazzi
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D006233:Persons with Disabilities; D018450:Disease Progression; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000000981:diagnostic imaging*; D059906:Neuroimaging / Q000379:methods
D015415:Biomarkers
Biomarker Score; Clinical disability; Energy-related serum metabolites; Mitochondrial dysfunction; Multiple sclerosis