Aerobic Exercise Training in Patients With mtDNA-Related Mitochondrial Myopathy

Abstract

In patients with mitochondrial DNA (mtDNA) mutation, a pathogenic mtDNA mutation is heteroplasmically distributed among tissues. The ratio between wild-type and mutated mtDNA copies determines the mtDNA mutation load of the tissue, which correlates inversively with oxidative capacity of the tissue. In patients with mtDNA mutation, the mutation load is often very high in skeletal muscle compared to other tissues. Additionally, skeletal muscle can increase its oxygen demand up to 100-fold from rest to exercise, which is unmatched by any other tissue. Thus, exercise intolerance is the most common symptom in patients with mtDNA mutation. The impaired oxidative capacity in skeletal muscle in patients with mtDNA mutation results in limitation in physical capacity that interferes with daily activities and impairs quality of life. Additionally, patients with mitochondrial disease due to mtDNA mutation often live a sedentary lifestyle, which further impair oxidative capacity and exercise tolerance. Since aerobic exercise training increase mitochondrial function and volume density in healthy individuals, studies have investigated if aerobic training could be used to counteract the progressive exercise intolerance in patients with mtDNA mutation. Overall studies investigating the effect of aerobic training in patients with mtDNA mutation have shown that aerobic training is an efficient way to improve oxidative capacity in this condition, and aerobic training seems to be safe even for patients with high mtDNA mutation in skeletal muscle.

Clinical presentation and natural history of Barth Syndrome: An overview

“…In a pilot study to study the effects of endurance exercise training in four individuals with BTHS, peak oxygen consumption modestly improved in three participants, however, resting heart function and skeletal muscle oxygen extraction during exercise did not improve. 57 It is not understood why the effects of aerobic training appear to be blunted when compared to other mitochondrial disorders, such as disorders caused by mtDNA mutations, where exercise is thought to improve mitochondrial mass and thus oxidative capacity, 58 but this may be due to the unique pathophysiology of CL deficiency, which extends beyond effects on the respiratory chain. In a separate pilot study to examine the effects of resistance training in three individuals with BTHS, a significant increase in strength in chest, biceps, and shoulder muscle groups were observed.…”

Mitochondriale Myopathien – Therapiemöglichkeiten durch Sport und Bewegung

“…Es ist bereits dokumentiert, dass Bewegungsprogramme von 8–48 Wochen 6 eine sichere therapeutische Option für Patienten mit mitochondrialer Myopathie darstellen. Es kommt dabei zur Steigerung der Phosphokreatinsynthese und zu einer Zunahme der mitochondrialen Enzyme, was zur Verbesserung klinischer Endpunkte wie Arbeitskapazität, Müdigkeit, Lebensqualität und Kraft führt.…”

Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs

“…Regular aerobic exercise, when possible, is suggested and was shown to enhance exercise tolerance and improve the fatigue MD common condition [ 31 , 32 ]. Similarly, surgical interventions for eyelid ptosis, another common manifestation in patients affected by MDs [ 33 ], can significantly improve patients’ quality of life.…”