Metabolomics in amyotrophic lateral sclerosis: how far can it take us?

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. Alongside identification of aetiologies, development of biomarkers is a foremost research priority. Metabolomics is one promising approach that is being utilized in the search for diagnosis and prognosis markers. Our aim is to provide an overview of the principal research in metabolomics applied to ALS. References were identified using PubMed with the terms 'metabolomics' or 'metabolomic' and 'ALS' or 'amyotrophic lateral sclerosis' or 'MND' or 'motor neuron disorders'. To date, nine articles have reported metabolomics research in patients and a few additional studies examined disease physiology and drug effects in patients or models. Metabolomics contribute to a better understanding of ALS pathophysiology but, to date, no biomarker has been validated for diagnosis, principally due to the heterogeneity of the disease and the absence of applied standardized methodology for biomarker discovery. A consensus on best metabolomics methodology as well as systematic independent validation will be an important accomplishment on the path to identifying the long-awaited biomarkers for ALS and to improve clinical trial designs.

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

“…Finally, one other biomarker discovery method is a comprehensive screening of metabolites in each of these biofluids pNFH = phosphorylated neurofilament heavy chain; CSF = cerebrospinal fluid; DC = diseased controls; MND = patients with motor neuron disease; HC = healthy controls; NFL = neurofilament light chain; IL = interleukin; GM-CSF = granulocyte macrophage colony-stimulating factor; p75NTR = neurotrophin receptor p75 [170]. Many untargeted metabolite studies have been previously performed in CSF [171,172], plasma [149,173], and serum [174], but metabolite identification is usually confined to searches using in-house databases, which biases the results.…”

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

“…Phenotypic heterogeneity and lack of diagnostic biomarkers pose difficulties in establishing the diagnosis in very early stages. Indeed, the interval time between the appearance of first symptoms and the diagnosis is more than 1 year and often, it is greater (Blasco et al, 2015(Blasco et al, , 2016.…”

Combined Metabolomics and Transcriptomics Approaches to Assess the IL-6 Blockade as a Therapeutic of ALS: Deleterious Alteration of Lipid Metabolism

“…Branched chain amino acid (BCAA) metabolism has been largely described in ALS, and we identified this way as potentially interesting for ALS diagnosis and prognosis in previous studies [64].…”