Open AccessMetabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers
Author(s) -
Buzkova Jana,
Nikkanen Joni,
Ahola Sofia,
Hakonen Anna H,
Sevastianova Ksenia,
Hovinen Topi,
YkiJärvinen Hannele,
Pietiläinen Kirsi H,
Lönnqvist Tuula,
Velagapudi Vidya,
Carroll Christopher J,
Suomalainen Anu
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809091
Subject(s) - mitochondrial myopathy , inclusion body myositis , creatine , mitochondrial disease , spinocerebellar ataxia , bioinformatics , medicine , myopathy , biology , biomarker , metabolome , disease , metabolomics , genetics , mitochondrial dna , gene
Mitochondrial disorders ( MD s) 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 MD s 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 NMD s. MD s and IBM showed transsulfuration pathway changes; creatine and niacinamide depletion marked NMD s, 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 MD s from others (76% sensitivity, 95% specificity). Our omics approach identified pathways currently used to treat NMD s and mitochondrial stroke‐like episodes and proposes nicotinamide riboside in MD s 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.