Physiotherapy, or the physical manipulation of joints and muscles for therapeutic purposes, is as old as medicine itself. In ancient societies, archeologists discovered that humanity has always applied the principle of “rest now, move later” when it comes to bone/muscular damage. 

Despite all the advancements we have made in medicine, this principle still rings largely true. The primary difference is that we now have means of imaging that allow us to survey the extent of bone/muscle damage in a way that allows for precision care.

Physiotherapy remains indispensable in treating diseases that cause muscle wasting, particularly when there is no cure, such as in the case of Pompe disease. In Pompe disease, patients suffer from a deficiency in the lysosomal enzyme acid alpha-glucosidase (GAA). This deficiency causes lysosomes to accumulate in the skeletal and heart muscle. The clinical manifestation of this disease is progressive myopathy, including respiratory difficulties at later stages of the disease. 

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The introduction of enzyme replacement therapy using recombinant human GAA has improved clinical outcomes; studies have demonstrated that it alleviates cardiomyopathy, but its impact on progressive muscle weakness is minimal. This means that enzyme replacement therapy cannot significantly alter the course of the disease with regards to muscle wasting. 

Improving Muscle Strength 

As published in Neuromuscular Disorders, Bhatnagar and colleagues conducted an insightful study into the effectiveness of resistance training in patients with late-onset Pompe disease. 

In late-onset Pompe disease, enzyme replacement therapy allows patients to initially gain some stabilization in their disease progress; however, clinical deterioration eventually picks up again and patients lose significant muscular strength. 

Read more about Pompe disease etiology

The same is true for respiratory function; enzyme replacement therapy provides relief for a period of time before clinical deterioration continues. 

Studies have suggested that exercise therapy can improve muscle deterioration, opening up a new form of recourse for patients with Pompe disease. Scientists have proposed that the benefits of exercise therapy are a result of enhanced autophagy and mitochondrial biogenesis, as opposed to the increased uptake of enzyme replacement therapy. 

Bhatnagar and colleagues set out to study the therapeutic effects of resistance training as adjunct therapy to enzyme replacement therapy to patients with late-onset Pompe disease. A 24-week resistance training program was prescribed for each patient (N=7). 

“The trainers were provided training on the exercise protocol and instructed on how to use the Borg scale to monitor relative perceived exertion and muscle pain,” Bhatnagar et al wrote. 

The patients’ muscle strength was measured using a variety of tools and parameters. The results showed that participants demonstrated a decline of the 6-minute walking test by only 1.7 m, compared to a decline of 11.6 m per year. Participants also demonstrated improvements in the muscle strength of the knee flexors and elbow extensors. 

“During [enzyme replacement therapy], patients remained more or less stable, indicating that training was the main driver behind the effects,” the research team wrote. 

Respiratory Function Training 

The result of the study above is one of the reasons physiotherapy is often prescribed as a form of treatment alongside enzyme replacement therapy for patients with Pompe disease. However, an event that typically causes mortality if untreated is loss of respiratory function. 

“Despite enzyme replacement therapy . . . respiratory muscle weakness often persists and remains a primary cause of morbidity and mortality in [late-onset Pompe disease],” Jones and colleagues wrote in Neuromuscular Disorders. “Respiratory weakness inleads to ineffective cough and reduced airway clearance, sleep-disordered breathing, and progressive respiratory insufficiency.” 

Jones et al conducted a 12-week respiratory muscle training program in a group of 22 individuals with late-onset Pompe disease. All patients were already on enzyme replacement therapy. The participants committed to a total of 9 visits to the Duke University Medical Center in Durham, North Carolina. 

The primary outcome of this study was the patient’s maximum inspiratory pressure. The results demonstrated that changes in maximum inspiratory pressure were higher in the treatment group compared to the control; however, these differences were not statistically significant. 

Read more about Pompe disease treatment 

A potential contributor to this outcome is that the variability among patients was larger than expected. Based on the standard deviation of the changes in the maximum inspiratory pressure, the variability in response was very high. Thus, the study lacked sufficient statistical power. In addition, the sample size was relatively small and the authors of the study found great variability in terms of the baseline characteristics of participants. 

However, in the study by Bhatnagar and colleagues, respiratory resistance training resulted in a statistically significant improvement in the maximum inspirational pressure by a mean of 8.5 cm H2O. 

“Recently inspiratory muscle training was shown to improve [maximum inspiratory pressure] and thereby stabilize and decelerate the decline of the diaphragm strength and was recommended to be offered to all [late onset Pompe disease] patients,” they wrote. 

Jones et al noted that patients with late-onset Pompe disease were highly motivated to participate in relevant clinical trials. This suggests that patients remain generally optimistic about what medicine can accomplish in improving their clinical outcomes. The onus is therefore on the scientific community to continue pursuing worthy threads of investigation in order to further turn the tide against Pompe disease.


Bhatnagar C, Shah J, Ramani B, et al. Safety and effectiveness of resistance training in patients with late onset Pompe disease – a pilot studyNeuromuscul Disord. 2022;32(4):284-294. doi:10.1016/j.nmd.2022.02.002

Jones HN, Kuchibhatla M, Crisp KD, et al. Respiratory muscle training in late-onset Pompe disease: results of a sham-controlled clinical trialNeuromuscul Disord. 2020;30(11):904-914. doi:10.1016/j.nmd.2020.09.023