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

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http://hdl.handle.net/10138/287671

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Buzkova , J , Nikkanen , J , Ahola , S , Hakonen , A H , Sevastianova , K , Hovinen , T , Yki-Järvinen , H , Pietiläinen , K H , Lönnqvist , T , Velagapudi , V , Carroll , C J & Suomalainen , A 2018 , ' Metabolomes of mitochondrial diseases and inclusion body myositis patients : treatment targets and biomarkers ' , EMBO molecular medicine , vol. 10 , no. 12 , 9091 . https://doi.org/10.15252/emmm.201809091

Title: Metabolomes of mitochondrial diseases and inclusion body myositis patients : treatment targets and biomarkers
Author: Buzkova, Jana; Nikkanen, Joni; Ahola, Sofia; Hakonen, Anna H.; Sevastianova, Ksenia; Hovinen, Topi; Yki-Järvinen, Hannele; Pietiläinen, Kirsi H.; Lönnqvist, Tuula; Velagapudi, Vidya; Carroll, Christopher J.; Suomalainen, Anu
Contributor: University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Anu Wartiovaara / Principal Investigator
University of Helsinki, Department of Medicine
University of Helsinki, Department of Medicine
University of Helsinki, Department of Medicine
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, Department of Neurosciences
Date: 2018-12
Language: eng
Number of pages: 15
Belongs to series: EMBO molecular medicine
ISSN: 1757-4676
URI: http://hdl.handle.net/10138/287671
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.
Subject: biomarker
inclusion body myositis
metabolomics
mitochondrial diseases
ONSET SPINOCEREBELLAR ATAXIA
RECESSIVE ATAXIA
DNA DELETIONS
MELAS
MUTATION
MYOPATHY
HYPERLACTATEMIA
METABOANALYST
PREVALENCE
DEFICIENCY
3111 Biomedicine
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