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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Cerebrospinal fluid ATP metabolites in multiple sclerosis
G Lazzarino1, A M Amorini, M J Eikelenboom
1Department of Chemical Sciences, Laboratory of Biochemistry, University of Catania, Italy.
Multiple Sclerosis (Houndmills, Basingstoke, England)
|March 3, 2010
Summary
Central ATP depletion in multiple sclerosis patients predicts greater disability progression. This finding suggests energy deficits may drive clinical worsening, independent of imaging or biomarker evidence of axonal damage.
Area of Science:
- Neuroscience
- Biochemistry
- Clinical Neurology
Background:
- Multiple sclerosis (MS) involves axonal degeneration and disability, potentially linked to energy deficits.
- Mitochondrial dysfunction and increased axonal energy demand are hypothesized contributors to MS pathology.
Purpose of the Study:
- To investigate if adenosine triphosphate (ATP) depletion precedes clinical, imaging, and biomarker signs of axonal degeneration in MS.
- To assess the relationship between central ATP metabolism and disease progression in multiple sclerosis patients.
Main Methods:
- A longitudinal study of 21 MS patients.
- Quantification of cerebrospinal fluid (CSF) ATP metabolites (oxypurines and purines) using high-performance liquid chromatography at baseline.
- Assessment of clinical disability (Expanded Disability Status Scale), brain atrophy (MRI), and CSF axonal damage biomarkers (neurofilaments) at baseline and 3-year follow-up.
Main Results:
- Central ATP depletion (>19.7 micromol/litre) was associated with more severe disability progression compared to normal ATP metabolite levels (p<0.05).
- Baseline ATP metabolite levels significantly correlated with changes in the Expanded Disability Status Scale in the overall cohort and specific MS subtypes (p<0.01).
- No correlation was found between central ATP metabolites and MRI or CSF biomarker evidence of axonal degeneration.
Conclusions:
- Increased energy demand in MS may lead to measurable central ATP depletion.
- Clinical disability progression in MS might be linked to ATP depletion-induced conduction block, rather than direct axonal damage detectable by current biomarkers or imaging.
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