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dc.contributor.authorSteele, Hannah
dc.contributor.authorGomez-Duran, Aurora
dc.contributor.authorPyle, Angela
dc.contributor.authorHopton, Sila
dc.contributor.authorNewman, Jane
dc.contributor.authorStefanetti, Renae J
dc.contributor.authorCharman, Sarah J
dc.contributor.authorParikh, Jehill D
dc.contributor.authorHe, Langping
dc.contributor.authorViscomi, Carlo
dc.contributor.authorJakovljevic, Djordje G
dc.contributor.authorHollingsworth, Kieren G
dc.contributor.authorRobinson, Alan J
dc.contributor.authorTaylor, Robert W
dc.contributor.authorBottolo, Leonardo
dc.contributor.authorHorvath, Rita
dc.contributor.authorChinnery, Patrick F
dc.date.accessioned2020-03-31T00:32:25Z
dc.date.available2020-03-31T00:32:25Z
dc.date.issued2020-02-28
dc.identifier.issn1757-4676
dc.identifier.otherPMC7059007
dc.identifier.other32107855
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303934
dc.descriptionFunder: Medical Research Council (MRC): Confidence in Concept award to Newcastle University
dc.description.abstractMitochondrial disorders affect 1/5,000 and have no cure. Inducing mitochondrial biogenesis with bezafibrate improves mitochondrial function in animal models, but there are no comparable human studies. We performed an open-label observational experimental medicine study of six patients with mitochondrial myopathy caused by the m.3243A>G MTTL1 mutation. Our primary aim was to determine the effects of bezafibrate on mitochondrial metabolism, whilst providing preliminary evidence of safety and efficacy using biomarkers. The participants received 600-1,200 mg bezafibrate daily for 12 weeks. There were no clinically significant adverse events, and liver function was not affected. We detected a reduction in the number of complex IV-immunodeficient muscle fibres and improved cardiac function. However, this was accompanied by an increase in serum biomarkers of mitochondrial disease, including fibroblast growth factor 21 (FGF-21), growth and differentiation factor 15 (GDF-15), plus dysregulation of fatty acid and amino acid metabolism. Thus, although potentially beneficial in short term, inducing mitochondrial biogenesis with bezafibrate altered the metabolomic signature of mitochondrial disease, raising concerns about long-term sequelae.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1757-4684
dc.sourcenlmid: 101487380
dc.subjectMitochondrial DNA
dc.subjectBezafibrate
dc.subjectMetabolomics
dc.subjectMitochondrial Disorder
dc.subjectMitochondrial Encephalomyopathy
dc.titleMetabolic effects of bezafibrate in mitochondrial disease.
dc.typeArticle
dc.date.updated2020-03-31T00:32:25Z
prism.issueIdentifier3
prism.publicationNameEMBO molecular medicine
prism.volume12
dc.identifier.doi10.17863/CAM.51018
rioxxterms.versionofrecord10.15252/emmm.201911589
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidGomez-Duran, Aurora [0000-0002-5895-6860]
dc.contributor.orcidViscomi, Carlo [0000-0001-6050-0566]
dc.contributor.orcidTaylor, Robert W [0000-0002-7768-8873]
dc.contributor.orcidBottolo, Leonardo [0000-0002-6381-2327]
dc.contributor.orcidHorvath, Rita [0000-0002-9841-170X]
dc.contributor.orcidChinnery, Patrick F [0000-0002-7065-6617]
pubs.funder-project-idMedical Research Council (MC_UU_00015/9, G1100160)
pubs.funder-project-idWellcome Trust (201064/Z/16/Z, 212219/Z/18/Z)
pubs.funder-project-idEuropean Research Council (201064, 309548)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International