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Monitoring Clinical Progression with Mitochondrial Disease Biomarkers

Accepted version

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Steele, HE 
Lyon, JJ 
Chinnery, PF 


Mitochondrial disorders are genetically determined metabolic diseases due to a biochemical deficiency of the respiratory chain. Given that multi-system involvement and disease progression are common features of mitochondrial disorders they carry substantial morbidity and mortality. Despite this, no disease-modifying treatments exist with clear clinical benefits, and the current best management of mitochondrial disease is supportive. Several therapeutic strategies for mitochondrial disorders are now at a mature preclinical stage. Some are making the transition into early-phase patient trials, but the lack of validated biomarkers of disease progression presents a challenge when developing new therapies for patients. This update discusses current biomarkers of mitochondrial disease progression including metabolomics, circulating serum markers, exercise physiology, and both structural and functional imaging. We discuss the advantages and disadvantages of each approach, and consider emerging techniques with a potential role in trials of new therapies.



biomarkers, mitochondrial disease, disease progression, mtDNA, mitochondrial encephalomyopathy

Journal Title

Brain; a journal of neurology

Conference Name

Journal ISSN


Volume Title



Oxford University Press
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Wellcome Trust (101876/Z/13/Z)
Wellcome Trust (101876/B/13/A)
Department of Health (via Newcastle University) (BH091682-RG81903)
Wellcome Trust (109915_A_15_Z)
P.F.C. is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/Z), and a UK NIHR Senior Investigator, who receives support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943), EU FP7 TIRCON, and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. R.H. is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z) and the Newton Fund (UK/Turkey, MR/N027302/1). GlaxoSmithKline provides support for H.E.S. as part of their Early Talent Review Board (ETRB) Clinical Fellow program.