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Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers.

Buzkova, J; Nikkanen, J; Ahola, S; Hakonen, AH; Sevastianova, K; Hovinen, T; Yki-Järvinen, H; Pietiläinen, KH; Lönnqvist, T; Velagapudi, V; et al. Buzkova, J; Nikkanen, J; Ahola, S; Hakonen, AH; Sevastianova, K; Hovinen, T; Yki-Järvinen, H; Pietiläinen, KH; Lönnqvist, T; Velagapudi, V; Carroll, CJ; Suomalainen, A (2018) Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers. EMBO Mol Med, 10 (12). e9091. ISSN 1757-4684 https://doi.org/10.15252/emmm.201809091
SGUL Authors: Carroll, Christopher John

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Abstract

Mitochondrial disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We investigated metabolomes of 25 mitochondrial myopathy or ataxias patients, 16 unaffected carriers, six IBM and 15 non-mitochondrial neuromuscular disease (NMD) patients and 30 matched controls. MD and IBM metabolomes clustered separately from controls and NMDs. MDs and IBM showed transsulfuration pathway changes; creatine and niacinamide depletion marked NMDs, IBM and infantile-onset spinocerebellar ataxia (IOSCA). Low blood and muscle arginine was specific for patients with m.3243A>G mutation. A four-metabolite blood multi-biomarker (sorbitol, alanine, myoinositol, cystathionine) distinguished primary MDs from others (76% sensitivity, 95% specificity). Our omics approach identified pathways currently used to treat NMDs and mitochondrial stroke-like episodes and proposes nicotinamide riboside in MDs and IBM, and creatine in IOSCA and IBM as novel treatment targets. The disease-specific metabolic fingerprints are valuable "multi-biomarkers" for diagnosis and promising tools for follow-up of disease progression and treatment effect.

Item Type: Article
Additional Information: © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: biomarker, inclusion body myositis, metabolomics, mitochondrial diseases, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: EMBO Mol Med
ISSN: 1757-4684
Language: eng
Dates:
DateEvent
1 December 2018Published
29 October 2018Published Online
24 September 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
272376European Research Councilhttp://dx.doi.org/10.13039/501100000781
PubMed ID: 30373890
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110462
Publisher's version: https://doi.org/10.15252/emmm.201809091

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