Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy

• Published in: Brain (London, England : 1878) Vol. 129; no. 12; pp. 3402 - 3412
• Main Authors: Jeppesen, Tina D., Schwartz, Marianne, Olsen, David B., Wibrand, Flemming, Krag, Thomas, Dunø, Morten, Hauerslev, Simon, Vissing, John
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2006; Oxford Publishing Limited (England)
• Subjects: Adult; Aerobiosis - physiology; Biological and medical sciences; Creatine Kinase - blood; Diseases of striated muscles. Neuromuscular diseases; DNA, Mitochondrial - genetics; Exercise Therapy - methods; Female; Gene Deletion; Heart Rate - physiology; Humans; Lactates - blood; Male; Medical sciences; Middle Aged; Mitochondria - enzymology; Mitochondrial Myopathies - genetics; Mitochondrial Myopathies - physiopathology; Mitochondrial Myopathies - therapy; mitochondrial myopathy; mtDNA; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Muscle, Skeletal - enzymology; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; mutation load; Neurology; Oxygen Consumption - physiology; Point Mutation - genetics; Quality of Life; training; Treatment Outcome; Physical exercise; Human; Nervous system diseases; mtDNA; Metabolic diseases; training; Enzymopathy; Congenital disease; Striated muscle disease; Mitochondria; mutation load; Mitochondrial myopathy; Mutation
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awl149

Exercise intolerance is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still unsettled whether exercise training is safe and beneficial for patients with MM. To address this, we studied the effect of 12 weeks cycle training on exercise capacity, quality of life and underlying molecular and cellular events in five patients with single large-scale deletions, one with a microdeletion and 14 with point mutations of mitochondrial DNA (mtDNA), and 13 healthy subjects. Each training session lasted 30 min, and was performed at an intensity of 70% of VO2max (maximal oxygen uptake). Each subject performed 50 training sessions in 12 weeks. All subjects were evaluated before and after training, and 13 MM patients were studied after 8 weeks of deconditioning. Evaluation included VO2max and mutation load and mtDNA quantity, mitochondrial enzymatic activity, and number of centrally nucleated, apoptotic, ragged red and cytochrome oxidase (COX)-negative fibres in muscle biopsies from the quadriceps muscle. After 12 weeks of training, VO2max and muscle citrate synthase increased in MM (26 and 67%) and healthy (17 and 65%) subjects, while mtDNA quantity in muscle only increased in the MM patients (81%). In the MM patients, training did not change mtDNA mutation load in muscle, mitochondrial enzyme complex activities, muscle morphology and plasma creatine kinase. After deconditioning, VO2max and citrate synthase activity returned to values before training, while muscle mtDNA mutation load decreased. These findings show that aerobic training efficiently improves oxidative capacity in MM patients. Based on unchanged levels of mutant load in muscle, morphological findings on muscle biopsy and plasma creatine kinase levels during training, the treatment appears to be safe. Regular, supervised aerobic exercise is therefore recommended in MM patients with the studied mutations.