There is no generally effective
therapy for
mitochondrial myopathies. In this study, we measured responses to combined aerobic training and oral dichloroacetate (DCA)
therapy in a 25-year-old woman with a
mitochondrial myopathy caused by
cytochrome oxidase deficiency. The patient trained for 14 weeks, and DCA
therapy was begun after 8 weeks. Independent indices of aerobic capacity and oxidative metabolism showed substantial improvement. Venous
lactate concentrations at rest, and after a constant amount of work, decreased by approximately 50% after 8 weeks of aerobic training, and by more than 70% with the combination of training and DCA treatment. Heart rate at rest and after a constant amount of submaximal work decreased progressively. Aerobic capacity on a graded submaximal exercise test improved by 71% from baseline by the end of the treatment period. 31P magnetic resonance spectroscopy measurements of rate constants for recovery of muscle
phosphocreatine increased 1.7-fold and metabolically active
adenine diphosphate increased 2.8-fold after 8 weeks of training alone, and 4.5-fold and 23.0-fold after 14 weeks of training plus DCA treatment. Responses to the SF-36 Health Survey suggested a marked reduction in handicap. Thus, in this open study of a patient with
cytochrome oxidase deficiency, a combination of aerobic training and DCA treatment resulted in substantial improvements in biochemical indices, exercise performance, and handicap. We conclude that exercise limitation in patients with
mitochondrial myopathy may arise from effects of chronic deconditioning in addition to the effects of primary
mitochondrial dysfunction and may be partially reversed by training and administration of DCA.