title: Metabolic dysfunctions in multiple sclerosis: implications as to causation, early detection, and treatment, a case control study.
abstract: BACKGROUND
  Biochemical changes associated with multiple sclerosis (MS), and its various clinical forms have not been characterized well. Therefore, we investigated the biochemistry of MS in relation to its natural history using targeted lipidomics platforms.
  
  
  METHODS
  Cross-sectional serum samples from 24 secondary progressive (SPMS), 100 relapsing remitting (RRMS), 19 primary progressive MS (PPMS), and 55 age-matched control subjects were analyzed by flow injection tandem mass spectrometry for very long chain fatty acid (VLCFA) containing phosphatidyl ethanolamines (PtdEtn), plasmalogen ethanolamines (PlsEtn) and for novel anti-inflammatory gastrointestinal tract acids (GTAs). Changes in analyte levels relative to healthy controls were correlated with the disease stage and disease duration.
  
  
  RESULTS
  RRMS subjects having <13 years disease duration had elevated levels (p < 0.05) of anti-inflammatory metabolites (GTAs) and normal levels (p > 0.05) of mitochondrial stress biomarkers (VLCFA-PtdEtn), compared to controls. SPMS subjects had statistically similar levels of anti-inflammatory metabolites (GTAs), elevated mitochondrial stress metabolites (VLCFA-PtdEtn) and elevated peroxisomal metabolites (PlsEtn) compared to controls (p < 0.05). RRMS subjects with > = 13 years disease duration exhibited metabolic profiles intermediate between short-duration RRMS and SPMS, based on statistical significance. Therefore, RRMS cohort appear to comprise of two metabolically distinct subpopulations. The key clinical discriminator of these two groups was disease duration. PPMS patients exhibited metabolic profiles distinct from RRMS and SPMS.
  
  
  CONCLUSIONS
  These data indicate that inflammation and mitochondrial stress are intricately involved in the etiology of MS and that progression in MS can potentially be monitored using serum metabolic biomarkers.
authors: Phenomenome Discoveries Inc, 204-407 Downey Road, Saskatoon, SK, S7N 4L8, Canada.
authors: Vijitha K
authors: VK
authors: Senanayake
authors: Phenomenome Discoveries Inc, 204-407 Downey Road, Saskatoon, SK, S7N 4L8, Canada.
authors: Wei
authors: W
authors: Jin
authors: Phenomenome Discoveries Inc, 204-407 Downey Road, Saskatoon, SK, S7N 4L8, Canada.
authors: Asuka
authors: A
authors: Mochizuki
authors: Phenomenome Discoveries Inc, 204-407 Downey Road, Saskatoon, SK, S7N 4L8, Canada.
authors: Bassirou
authors: B
authors: Chitou
authors: Phenomenome Discoveries Inc, 204-407 Downey Road, Saskatoon, SK, S7N 4L8, Canada. d.goodenowe@phenomenome.com.
authors: Dayan B
authors: DB
authors: Goodenowe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood*; D010714:Phosphatidylethanolamines / Q000097:blood; D010955:Plasmalogens / Q000097:blood; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D010714:Phosphatidylethanolamines; D010955:Plasmalogens