Contributions
Abstract: P949
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Multiple sclerosis (MS) is an inflammatory demyelinating disease but the underlying cause as well as the pathological processes, are poorly understood. We used metabolomics to investigate the changes in the cellular and biochemical pathways associated with MS.
In the current study, we conducted a targeted quantitative validated metabolomic screen using the AbsoluteIDQ p180 assay (Biocrates Life Sciences AG). The mass spectrometric-based assay involved the comprehensive identification and quantification of more than 186 endogenous metabolite classes including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingolipids, ceramides, and monosaccharides. Cerebrospinal fluid (CSF) was collected from 120 MS patients and 30 age- and sex-matched controls with informed consent under an IRB-approved protocol. Statistical analysis was done to identify the significantly altered metabolites. The analysis revealed 40 single metabolites and 11 markers/ratios that are altered more than a fold in the MS population as compared to the control. The significantly altered metabolic pathways include those involved in aromatic amino acid, branched chain amino acid, phosphatidylcholine, sphingomyelin and methionine metabolism. Furthermore, the metabolite changes clearly show correlations with disease stage and activity. Interestingly, the revealed perturbations in the CSF metabolome are both consistent and different when comparing MS patients at different clinical stages (relapsing remitting vs. progressive) and allow stratification. The animal model of MS - EAE, was next used to further investigate the effect of these metabolic pathways on disease pathology. In our initial studies using western blotting and ELISA, we found increased levels of the methionine sulfoxide in the spinal cord and brain lysates from EAE mice as compared to control mice. Methionine sulfoxide dose dependently decreased the cell viability of neuroblastoma cells which was further exacerbated by methionine deprivation. We also detected increased secretory phospholipase A2 activity, in the EAE mice at disease peak. Taken together the results provide tantalizing clues about the pathogenesis of MS with marked changes in energy metabolism, lipid and amino acid dynamics.
Disclosure:
Fozia Mir: Nothing to disclose
Zerina Balic: Nothing to disclose
Jeffrey Jian: Nothing to disclose
Saud A. Sadiq: Nothing to disclose
Abstract: P949
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Multiple sclerosis (MS) is an inflammatory demyelinating disease but the underlying cause as well as the pathological processes, are poorly understood. We used metabolomics to investigate the changes in the cellular and biochemical pathways associated with MS.
In the current study, we conducted a targeted quantitative validated metabolomic screen using the AbsoluteIDQ p180 assay (Biocrates Life Sciences AG). The mass spectrometric-based assay involved the comprehensive identification and quantification of more than 186 endogenous metabolite classes including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingolipids, ceramides, and monosaccharides. Cerebrospinal fluid (CSF) was collected from 120 MS patients and 30 age- and sex-matched controls with informed consent under an IRB-approved protocol. Statistical analysis was done to identify the significantly altered metabolites. The analysis revealed 40 single metabolites and 11 markers/ratios that are altered more than a fold in the MS population as compared to the control. The significantly altered metabolic pathways include those involved in aromatic amino acid, branched chain amino acid, phosphatidylcholine, sphingomyelin and methionine metabolism. Furthermore, the metabolite changes clearly show correlations with disease stage and activity. Interestingly, the revealed perturbations in the CSF metabolome are both consistent and different when comparing MS patients at different clinical stages (relapsing remitting vs. progressive) and allow stratification. The animal model of MS - EAE, was next used to further investigate the effect of these metabolic pathways on disease pathology. In our initial studies using western blotting and ELISA, we found increased levels of the methionine sulfoxide in the spinal cord and brain lysates from EAE mice as compared to control mice. Methionine sulfoxide dose dependently decreased the cell viability of neuroblastoma cells which was further exacerbated by methionine deprivation. We also detected increased secretory phospholipase A2 activity, in the EAE mice at disease peak. Taken together the results provide tantalizing clues about the pathogenesis of MS with marked changes in energy metabolism, lipid and amino acid dynamics.
Disclosure:
Fozia Mir: Nothing to disclose
Zerina Balic: Nothing to disclose
Jeffrey Jian: Nothing to disclose
Saud A. Sadiq: Nothing to disclose