COMBINED AEROBIC TRAINING AND DICHLOROACETATE IMPROVE EXERCISE CAPACITY AND INDEXES OF AEROBIC METABOLISM IN MUSCLE CYTOCHROME-OXIDASE DEFICIENCY

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 mitoc hondrial myopathy caused by cytochrome oxidase deficiency. The patient trained for 14 weeks, and DCA therapy was begun after 8 weeks. Indepe ndent indices of aerobic capacity and oxidative metabolism showed subs tantial improvement. Venous lactate concentrations at rest, and after a constant amount of work, decreased by approximately 50% after 8 week s of aerobic training, and by more than 70% with the combination of tr aining and DCA treatment. Heart rate at rest and after a constant amou nt of submaximal work decreased progressively. Aerobic capacity on a g raded submaximal exercise test improved by 71% from baseline by the en d of the treatment period. P-31 magnetic resonance spectroscopy measur ements of rate constants for recovery of muscle phosphocreatine increa sed 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 aft er 14 weeks of training plus DCA treatment. Responses to the SF-36 Hea lth Survey suggested a marked reduction in handicap. Thus, in this ope n study of a patient with cytochrome oxidase deficiency, a combination of aerobic training and DCA treatment resulted in substantial improve ments in biochemical indices, exercise performance, and handicap. We c onclude that exercise limitation in patients with mitochondrial myopat hy may arise from effects of chronic deconditioning in addition to the effects of primary mitochondrial dysfunction and may be partially rev ersed by training and administration of DCA.