Metabolic and Muscle Adaptation to Aerobic Training in Patients Affected by Chronic Progressive External Ophthalmoplegia

Mitochondrial myopathies with respiratory chain defects are multisystem diseases characterised by mitochondrial DNA (mtDNA) mutations responsible for impairment of aerobic cell metabolism. At the skeletal muscle level involvement of respiratory chain function is the cause of insufficient ATP production and deranged metabolism, a main effect of which is represented by abnormal production of lactate. Recently, it has been reported beneficial effects of aerobic training on muscle performance in mitochondrial myopathy subjects. Aim of this study was to evaluate in 9 patients affected by chronic progressive external ophthalmoplegia (CPEO) and large-scale mtDNA rearrangements functional adaptation of skeletal muscle to aerobic training, and to relate it to muscle biopsies parameters assessed before the training. To this purpose, CPEO patients underwent an exercise test performed at the anaerobic lactate threshold before and after a supervised 10-week course of aerobic training. A correlation was found between the training-related decrement in exercise peak lactate and cytochrome c oxidase (COX) enzyme activity (inverse correlation, r=-0.81, p<0.05), and with the number of COX(r=0.72, p<0.05) and ragged red fibers (r=0.64, p=0.05). On the contrary, no relation was found with the amount of deleted mtDNA in muscle biopsy. These results indicate that aerobic training can be beneficial also in those CPEO patients more severely affected by mitochondrial dysfunction. The level of COX activity in muscle biopsy rather than the amount of mutated mtDNA seems to be a useful predictor for the effectiveness of aerobic training program, suggesting some gene expression mechanisms in mediating muscle adaptation to training itself in these patients.