Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers
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 pa...
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201809091 |
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| author | Jana Buzkova Joni Nikkanen Sofia Ahola Anna H Hakonen Ksenia Sevastianova Topi Hovinen Hannele Yki‐Järvinen Kirsi H Pietiläinen Tuula Lönnqvist Vidya Velagapudi Christopher J Carroll Anu Suomalainen |
| author_facet | Jana Buzkova Joni Nikkanen Sofia Ahola Anna H Hakonen Ksenia Sevastianova Topi Hovinen Hannele Yki‐Järvinen Kirsi H Pietiläinen Tuula Lönnqvist Vidya Velagapudi Christopher J Carroll Anu Suomalainen |
| author_sort | Jana Buzkova |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-719edba7c7e845febe3924c436b1d7a2 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2018-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-719edba7c7e845febe3924c436b1d7a22025-08-20T04:03:02ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-10-01101211510.15252/emmm.201809091Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkersJana Buzkova0Joni Nikkanen1Sofia Ahola2Anna H Hakonen3Ksenia Sevastianova4Topi Hovinen5Hannele Yki‐Järvinen6Kirsi H Pietiläinen7Tuula Lönnqvist8Vidya Velagapudi9Christopher J Carroll10Anu Suomalainen11Research Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiResearch Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiResearch Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiResearch Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiDepartment of Medicine, University of Helsinki and Helsinki University HospitalResearch Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiDepartment of Medicine, University of Helsinki and Helsinki University HospitalResearch Programs Unit, Diabetes and Obesity, Obesity Research Unit, University of HelsinkiDepartment of Child Neurology, Children′s Hospital, University of HelsinkiMetabolomics Unit, Institute for Molecular Medicine Finland FIMM, HiLIFE, University of HelsinkiResearch Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiResearch Programs Unit, Molecular Neurology, Biomedicum‐Helsinki, University of HelsinkiAbstract 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.https://doi.org/10.15252/emmm.201809091biomarkerinclusion body myositismetabolomicsmitochondrial diseases |
| spellingShingle | Jana Buzkova Joni Nikkanen Sofia Ahola Anna H Hakonen Ksenia Sevastianova Topi Hovinen Hannele Yki‐Järvinen Kirsi H Pietiläinen Tuula Lönnqvist Vidya Velagapudi Christopher J Carroll Anu Suomalainen Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers EMBO Molecular Medicine biomarker inclusion body myositis metabolomics mitochondrial diseases |
| title | Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers |
| title_full | Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers |
| title_fullStr | Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers |
| title_full_unstemmed | Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers |
| title_short | Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers |
| title_sort | metabolomes of mitochondrial diseases and inclusion body myositis patients treatment targets and biomarkers |
| topic | biomarker inclusion body myositis metabolomics mitochondrial diseases |
| url | https://doi.org/10.15252/emmm.201809091 |
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