As the medical world has made tremendous progress in many disease areas over the last decade, it has become a sort of cry in the wilderness for some physicians to remind the medical community about the good old virtues of diet and lifestyle modifications in supporting recovery from most diseases.
Indeed, research has time and again confirmed to us that simple lifestyle changes such as healthier dietary choices, regular exercise, and smoking cessation can make a big difference in the long run. In rare diseases in which a definitive cure is unavailable, lifestyle changes may be a patient’s best shot at achieving a quality of life as close to normal as possible.
Duchenne muscular dystrophy (DMD) is part of a group of progressive muscular dystrophies in which the muscles gradually waste away, eventually affecting the respiratory muscles and causing death. Most experimental therapies for DMD are focused on delaying disease progression and are not intended to be curative in themselves.
Physiotherapy plays a major role in managing DMD, particularly in strengthening weak muscles through exercises. The question is, how far can strengthening exercises go in making a notable difference in the lives of patients with DMD? We will attempt to answer this question by looking first at studies in mouse models and then at those in human participants.
Of Mice and Men
Hoepers and colleagues conducted a fascinating study into how low-intensity exercise affected X-linked muscular dystrophy (mdx) mouse models. They used mdx mice, with wild-type (wt) mouse models as the control, and divided them into 4 categories:
- Wt nonexercised
- Wt exercised
- Mdx nonexercised
- Mdx exercised
The animals in the exercise group were subjected to an aerobic training protocol for 8 weeks. The aerobic training protocol involved the mice being on a non-inclined treadmill with a preadjusted speed and time (30 minutes). Twenty-four hours after the final day of exercise, “the animals underwent painless death, and the gastrocnemius muscle and prefrontal cortex, cerebellum, hippocampus, striatum, and total cortex were removed” and the samples were “isolated for further analysis,” according to the authors of the study.
Read more about DMD epidemiology
The researchers found evidence of oxidative stress and a decrease in antioxidant activity in the nonexercised group of mdx mice. They also observed activity changes in the mitochondrial structure and an increase in creatine kinase in this group. These observations are relevant because oxidative stress and energy metabolism activity are important in the pathophysiology of DMD.
Meanwhile, in the exercised group of mdx mice, researchers observed a reversal of lipid and protein damage in the gastrocnemius muscle, as well as a significant increase in the antioxidant activity of glutathione compared to the nonexercised mdx group. The researchers also discovered that exercise was able to restore creatine kinase activity to normal parameters in the exercised group of mdx mice compared to the nonexercised mdx mice.
In a separate study, Lott and colleagues studied the effects of a mild to moderate resistance isometric leg program on ambulatory boys with DMD. To determine the appropriate level of exercise for each participant, the research team used a “dose-escalation” method of varying intensity and frequency of leg isometric exercise and determined safety through 3 parameters: magnetic resonance imaging (MRI) of leg muscles (T2 MRI), serum creatine kinase, and pain rating. They also determined the peak strength of the knee extensors and flexors of the right leg in each participant.
Read more about DMD treatment
Lott et al then sought to determine the safety and feasibility of a 12-week, in-home, mild- to moderate-intensity exercise program that was remotely supervised. The exercise program involved the boys exercising both legs 3 days per week for about 1.5 hours per session. The same 3 parameters of safety were measured.
The results were promising. Of the 8 boys who participated in the study, 7 completed the 12-week home exercise program. The compliance rate was 89.4%. In addition, the safety parameters demonstrated that this program was safe and effective in maintaining muscle strength. T2 MRI indicated no muscle damage. The researchers also discovered that the participants showed improvements in the strength of their knee extensors and flexors as well as in functional ability (descending stairs).
Strength and Safety
Lott et al commented, “The current study, in conjunction with previous studies, supports the notion that appropriately dosed strengthening exercise has the potential to improve strength and ability to descend stairs while being safe for boys with DMD.”
Indeed, it is important to remember the benefits of sustained, appropriately prescribed exercise in delaying disease progression in patients with DMD, as well as strengthening remaining muscles. The goal is to give patients with DMD the best chance to retain their ambulatory abilities for as long as possible.
Lott and colleagues wrote that the “early exploratory studies assessing the value of exercise in DMD showed that strengthening exercise had a positive effect on strength with no evidence for overload weakness nor physical deterioration, and advocated for starting exercise early in the course of the disease when there is a maximum amount of functional activity.”
This, unfortunately, did not translate into advancements in the application of strength exercise for boys with DMD. It is high time that this changes and that physical exercise is encouraged heartily by physicians, with both the benefits and limitations thoroughly explained to the patient.
Lott DJ, Taivassalo T, Cooke KD, et al. Safety, feasibility, and efficacy of strengthening exercise in Duchenne muscular dystrophy. Muscle Nerve. 2021;63(3):320-326. doi:10.1002/mus.27137
Hoepers A, Alberti A, Freiberger V, et al. Effect of aerobic physical exercise in an animal model of Duchenne muscular dystrophy. J Mol Neurosci. 2020;70(10):1552–1564. doi:10.1007/s12031-020-01565-0