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Cerebrospinal fluid ATP metabolites in multiple sclerosis

Lazzarino, G; Amorini, AM; Eikelenboom, MJ; Killestein, J; Belli, A; Di Pietro, V; Tavazzi, B; ... Petzold, A; + view all (2010) Cerebrospinal fluid ATP metabolites in multiple sclerosis. Multiple Sclerosis , 16 (5) 549 - 554. 10.1177/1352458510364196. Green open access

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Abstract

Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis.Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis.The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up.Central ATP depletion (sum of ATP metabolites >19.7 mu mol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p<0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort (r=0.66, p=0.001) and subgroups (relapsing-remitting patients: r=0.79, p<0.05 and secondary progressive/primary progressive patients: r=0.69, p<0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration.The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.

Type: Article
Title: Cerebrospinal fluid ATP metabolites in multiple sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/1352458510364196
Publisher version: http://dx.doi.org/10.1177/1352458510364196
Language: English
Keywords: Neurofilament phosphoforms, multiple sclerosis, prognosis, disease subtype, disability, axonal injury, NITRIC-OXIDE, MITOCHONDRIAL DYSFUNCTION, CELL-DEATH, AXONS, DEPLETION, SODIUM, MS, DEGENERATION, PROGRESSION, MECHANISMS
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/19874
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