Brain Advance Access originally published online on November 3, 2006
Brain 2006 129(12):3391-3401; doi:10.1093/brain/awl282
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Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions
1 Department of Kinesiology, McGill University Montreal, Quebec, Canada 2 Mitochondrial Research Group, School of Neurology Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK 3 Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital Dallas, TX, USA 4 University of Texas Southwestern Medical Center and VA Medical Center Dallas, TX, USA
Correspondence to: Prof. D. M. Turnbull, Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, Newcastle University, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK E-mail: d.m.turnbull{at}ncl.ac.uk
At present there are limited therapeutic interventions for patients with mitochondrial myopathies. Exercise training has been suggested as an approach to improve physical capacity and quality of life but it is uncertain whether it offers a safe and effective treatment for patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. The objectives of this study were to assess the effects of exercise training and detraining in eight patients with single, large-scale mtDNA deletions to determine: (i) the efficacy and safety of endurance training (14 weeks) in this patient population; (ii) to determine the effect of more prolonged (total of 28 weeks) exercise training upon muscle and cardiovascular function and (iii) to evaluate the effect of discontinued training (14 weeks) upon muscle and cardiovascular function. Our results show that: (i) 14 weeks of exercise training significantly improved tolerance of submaximal exercise and peak capacity for work, oxygen utilization and skeletal muscle oxygen extraction with no change in the level of deleted mtDNA; (ii) continued training for an additional 14 weeks maintained these beneficial adaptations; (iii) the cessation of training (detraining) resulted in loss of physiological adaptation to baseline capacity with no overall change in mutation load. Patients' self assessment of quality of life as measured by the SF-36 questionnaire improved with training and declined with detraining. Whilst our findings of beneficial effects of training on physiological outcome and quality of life without increases in the percentage of deleted mtDNA are encouraging, we did not observe changes in mtDNA copy number. Therefore there remains a need for longer term studies to confirm that endurance exercise is a safe and effective treatment for patients with mitochondrial myopathies. The effects of detraining clearly implicate physical inactivity as an important mechanism in reducing exercise capacity and quality of life in patients with mitochondrial myopathy.
Key Words: mitochondrial myopathy; deletions; exercise training
Abbreviations: COX, cytochrome c oxidase; mtDNA, mitochondrial DNA; RPE, ratings of perceived exertion; SDH, succinate dehydrogenase
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Received April 5, 2006. Revised August 21, 2006. Accepted September 4, 2006.
*These authors contributed equally to this work
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