Dr Débora Lanznaster - Combined Metabolomics and targeted-transcriptomics analysis in the muscle of early-stage ALS patients.
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons, leading to paralysis and death of patients after 3-5 years of symptoms’ onset. While skeletal muscle is severely attained in ALS patients, few studies analysed the pathological and metabolic alterations taking place in the muscle. By applying a broad metabolomics analysis, we demonstrated a very discriminant metabolomic profile of the muscle of early-stage ALS patients compared to controls. Further analysis of the most discriminant metabolites highlighted a major impact in several metabolic pathways such as amino acids metabolism, biosynthesis and degradation, aminoacyl-tRNA biosynthesis and the metabolism of glyoxylate and dicarboxylate. Multivariate analysis showed that muscle metabolome was associated with weight variation, while C10-carnitine levels were associated with survival. A targeted transcriptomics approach revealed increased levels of two major genes involved in the antioxidant response, SOD3 and GLRX2. Our broad metabolomics analysis combined with targeted transcriptomics revealed pathological alterations in the muscle of early-stage ALS patients that could be applied in the clinic as biomarkers for diagnosis and prognosis. Furthermore, these alterations represent new targets for the development of therapies to improve the clinical management of ALS patients.
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