Metabolic effects of bezafibrate in mitochondrial disease.

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dc.creatorSteele, Hannah
dc.creatorGomez-Duran, Aurora
dc.creatorPyle, Angela
dc.creatorHopton, Sila
dc.creatorNewman, Jane
dc.creatorStefanetti, Renae J
dc.creatorCharman, Sarah J
dc.creatorParikh, Jehill D
dc.creatorHe, Langping
dc.creatorViscomi, Carlo
dc.creatorJakovljevic, Djordje G
dc.creatorHollingsworth, Kieren G
dc.creatorRobinson, Alan J
dc.creatorTaylor, Robert W
dc.creatorBottolo, Leonardo
dc.creatorHorvath, Rita
dc.creatorChinnery, Patrick F
dc.date2020-02-01T00:32:21Z
dc.date2020-02-01T00:32:21Z
dc.date2020-03-06
dc.date.accessioned2026-08-03T04:33:05Z
dc.descriptionMitochondrial 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.descriptionWellcome Trust MRC
dc.formatPrint-Electronic
dc.formatapplication/pdf
dc.formatapplication/vnd.openxmlformats-officedocument.wordprocessingml.document
dc.formatimage/jpeg
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dc.identifier1757-4676
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/301602
dc.identifier10.17863/CAM.48671
dc.identifier1757-4684
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/190747
dc.languageeng
dc.languageeng
dc.publisherSpringer Nature
dc.publisherhttps://doi.org/10.15252/emmm.201911589
dc.rightsAttribution 4.0 International (CC BY)
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectbezafibrate
dc.subjectmetabolomics
dc.subjectmitochondrial DNA
dc.subjectmitochondrial disorder
dc.subjectmitochondrial encephalomyopathy
dc.subjectBezafibrate
dc.subjectHumans
dc.subjectMitochondria
dc.subjectMitochondrial Myopathies
dc.subjectOrganelle Biogenesis
dc.titleMetabolic effects of bezafibrate in mitochondrial disease.
dc.typeArticle

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