Endurance training as a treatment approach for Huntington’s disease

Huntington’s disease is a rare, inherited neurodegenerative disorder that progressively impairs motor and cognitive functions. It was previously thought that exercise might act as a stressor, accelerating disease progression; but now increased knowledge of the underlying mechanisms of the disease has led to new research suggesting that endurance exercise may actually have therapeutic potential for rare diseases like Huntington’s.

Huntington’s disease (HD) is an inherited, progressive neurodegenerative disorder. The disease is caused by the breakdown of neuronal cells in the central nervous system. During the course of the disease, motor, cognitive, psychological, and behavioral function are progressively impaired. The functional decline results in limitations during everyday life, leading to complete dependence on caregivers during the late stages of the disease.

HD usually results in death 15 to 20 years after symptom onset. In European countries, HD is most prevalent with 10 to 15 in 100,000 individuals affected by the disease. To date, there is still no causative treatment for HD. Medication and treatment serves its role in alleviating specific symptoms of the disease, but the overall course of disease is inexorable.

Based on the observation that stress might accelerate the progression of the disease, it was often proposed that patients should reduce all kind of stressors. Therefore, physical activity was considered to be a negative influencing factor and patients were advised not to participate in physical activity or sports. It was thereby assumed that the well-known protective functions of physical activity in healthy people were not transferable to this patient cohort.

Exploring endurance training effects on Huntington’s disease patients

In recent years, studies on the underlying mechanisms of HD elicited that peripheral factors of the disease include decreases in the mitochondrial function and thereby impairments in the cellular energy metabolism. For example, we could show in a previous study that mitochondrial respiratory capacity is impaired in HD patients when compared to healthy controls. Since it is well known that physical activity is a main factor in increasing skeletal muscle mitochondrial function in healthy individuals, the question arose whether the skeletal muscle of HD patients is also responsive to an endurance training stimulus.

In our current study, we show that mitochondrial content and muscle fiber capillarization increased following a 26-weeks endurance training intervention in Huntington’s disease patients.

In our current study, we show that mitochondrial content and muscle fiber capillarization increased following a 26-weeks endurance training intervention in HD patients. Irrespective of the lower baseline values, HD patients showed a similar trainability of their skeletal muscle fibers when compared to their healthy counterparts.

In a previous publication, we have already shown that the natural disease progression of motor function might be alleviated and physical performance is increased following an endurance training intervention in HD patients. However, so far our sample sizes have been too small to draw any conclusions about the effects of endurance training on neuropsychological factors in HD patients.

Effects of endurance training on other rare diseases

Based on our promising preliminary results on the effects of endurance training in rare diseases, we investigated in a parallel pilot study the effects of endurance training in patients with mitochondrial myopathies. As the name implies, these diseases are based on declines of mitochondrial function and are characterized, among other factors, by muscular weakness and exercise intolerance. Our results revealed that a period of high-intensity interval training resulted in a higher mitochondrial quantity and improved exercise capacity in patients with mitochondrial myopathies.

In summary, our studies revealed that endurance training is a safe and valuable treatment for the improvement of energy metabolism in rare diseases. On a muscular level, the training interventions resulted in increased mitochondrial content and improved aerobic energy metabolism. On a systemic level, endurance training improved physical fitness and self-reported quality of life of the patients.

Our studies shed light on the potential therapeutic effects of endurance training in rare diseases. We therefore suggest further investigation of the effects of endurance training in several muscular diseases. Furthermore, we recommend including endurance training as a treatment approach in HD and mitochondrial myopathies.

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