title: Biochemical alterations associated with ALS.
abstract: Our objective was to identify metabolic pathways affected by ALS using non-targeted metabolomics in plasma, comparing samples from healthy volunteers to those from ALS patients. This discovery could become the basis for the identification of therapeutic targets and diagnostic biomarkers of ALS. Two distinct cross-sectional studies were conducted. Plasma was collected from 62 (Study 1) and 99 (Study 2) participants meeting El Escorial criteria for possible, probable, or definite ALS; 69 (Study 1) and 48 (Study 2) healthy controls samples were collected. Global metabolic profiling was used to detect and evaluate biochemical signatures of ALS. Twenty-three metabolites were significantly altered in plasma from ALS patients in both studies. These metabolites include biochemicals in pathways associated with neuronal change, hypermetabolism, oxidative damage, and mitochondrial dysfunction, all of which are proposed disease mechanisms in ALS. The data also suggest possible hepatic dysfunction associated with ALS. In conclusion, the data presented here provide insight into the pathophysiology of ALS while suggesting promising areas of focus for future studies. The metabolomics approach can generate novel hypotheses regarding ALS disease mechanisms with the potential to identify therapeutic targets and novel diagnostic biomarkers.
authors: Metabolon Inc., North Carolina, USA.
authors: Kay A
authors: KA
authors: Lawton
authors: Merit E
authors: ME
authors: Cudkowicz
authors: Meredith V
authors: MV
authors: Brown
authors: Danny
authors: D
authors: Alexander
authors: Rebecca
authors: R
authors: Caffrey
authors: Jacob E
authors: JE
authors: Wulff
authors: Robert
authors: R
authors: Bowser
authors: Robert
authors: R
authors: Lawson
authors: Matt
authors: M
authors: Jaffa
authors: Michael V
authors: MV
authors: Milburn
authors: John A
authors: JA
authors: Ryals
authors: James D
authors: JD
authors: Berry
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use; D019782:Riluzole / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D019782:Riluzole