Exercise as it relates to Disease/Can aerobic and resistance training benefit late-onset Pompe disease patients undergoing enzyme replacement therapy (ERT)?
What is the background to this research?
Pompe disease, or glycogen storage disease type II, is an inherited autosomal recessive disease. It is caused by total or partial deficiency of acid α-glucosidase (GAA), an enzyme responsible for glycogenolysis. Deficiency results in the accumulation of glycogen in the lysosomes of skeletal muscles, heart, liver and other tissues. There are two distinct forms of the disease, infant-onset and adult or late-onset.
Late-onset Pompe disease is the less-severe form of the disease, it displays various clinical features. Symptoms at onset are displayed in table 1. (1)
| Symptoms at rest |
|---|
| Progressive walking limitations |
| Diffuse myalgias, muscle cramps |
| Intolerance to exercise |
| Frequent falls |
| Recurrent pulmonary infections |
| Dyspnea on exertion |
| Heart rhythm distrubances |
| Daytime sleepiness |
| Weightloss |
| Elevated creatine kinase (CK) levels |
The disease is progressive, and variable between patients. All patients will experience progressive muscle atrophy and weakness, especially in lower limbs. Some individuals may maintain a relatively independent lifestyle, while others often become wheelchair-bound. In any form, this is a disease that greatly reduces physical capability and independence.
The research conducted in this study is relatively new. Late-onset Pompe disease is rare, affecting ~1 in 58,000 per year (1). Furthermore, the enzyme replacement treatment (ERT) was only introduced in 2006 (2). The article points to and references only 1 comparable study into the treatment of late-onset Pompe disease with well-structured exercise (3). The authors regularly make reference to the absence of significant research in this selected field.
There is significant demand for treatment and managing of the disease for those suffering from late-onset Pompe disease. Increasing muscle function and functional capacity increase independence and standard of living for those affected. Exercise is cheap and manageable treatment, reducing individual cost and healthcare burden.
Where is the research from?
This study was published in the Molecular Genetics and Metabolism journal. The journal publishes articles describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. It is the official journal of the Society for Inherited Metabolic Disorders (SIMD). SIMD was established in 1978, their aim is to increase knowledge of and to promote research in inborn errors of metabolism in humans and to stimulate interactions between clinicians and investigators in inborn errors of metabolism.
The authors of this study are from Greece. They collectively represent The University of Athens, The University of Thrace and Eginition Hospital.
What kind of research was this?
The research undertaken is a clinical trial that evaluates treatment, in this case exercise, by observing participant outcomes on a prescribed schedule. The schedule being a 20 week long prescribed, monitored and professionally delivered exercise program.
What did the research involve?
Firstly, the approval for the study was secured from the Ethics Committee of the Eginition University Hospital. The authors then gained written consent from five individuals clinically diagnosed with late-onset Pompe disease. Participants were then taken through tests to determine baseline data. This testing procedure is standardised, highly replicable and adequately assesses it's set aims.
1. Maximum isometric strength was determined in a laboratory setting with the use of a Tesys 800, Globus Sport and Health Technologies load transducer set at a known resistance.
2. Body composition was determined using a DEXA scan, the gold standard for anthropometry.
3. Functional capacity was assessed with a 6-minute walking test (6MWT).
Following this, participants were taken through their exercise program with the supervision of a qualified and suitable instructor 3 days per week at home. The exercise program in its duration is shown below in table 2.
| Exercise | Header text | Header text |
|---|---|---|
| Bicycling | 0–15 min, level 1–2/8 | 30 min, level 2–4/8 |
| Stretching | Moderate range of movement | |
| ¼ Squat | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Leg curl | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Knee raise | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Push-ups against a wall | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Sit ups | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Back extensions | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| ¼ Overhead press | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Elbow extensions | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Elbow curl | 1–2 sets/10 reps/50% 10 RM | 3 sets/10 reps/50% 10 RM |
| Stretching | Moderate range of movement |
In order to gauge the effect of this training program on maximum isometric strength, body composition and functional capacity, the same initial tests were conducted. Data was collected and compared using statistical analysis. Paired t-tests were used to identify differences from pre to post training program results. The Pearson's r product moment correlation coefficient allowed the relationships between variables to be assessed. A two-tailed probability value of less than 0.05 was deemed significant. Statistical analysis was carried out with SPSS version 15.0.
What were the basic results?
The results of this study were largely positive. There were significant increases in maximum isometric strength in all of the strength tests across all participants. Functional capacity also improved, with significantly increased performance in the 6MWT. In anthropometry, bone density was unchanged, there was no significant decrease in body fat. A significant increase in lean body mass (LBM) of the upper-extremities was found. No significant increase in upper-extremity LBM was found.
In terms of correlations, there was a positive correlation between GAA and LBM in the lower body. This correlation was statistically significant in the upper body. A significant correlation was not found between lower-extremity strength and 6MWT. Correlation coefficients were significant between LBM and maximum isometric strength.
What conclusions can we take from this research?
The study has shown that tailored and prescribed exercise can be a useful means of increasing muscular strength and functional capacity for late-onset Pompe disease patients. These benefits were experienced by all participants and should be looked upon as a success. The exercise program did not yield effects upon body composition.
The reliability of this study would improve with an increased sample size. There is a clear lack of research on this topic and further studies should be conducted. The results of this study are encouraging and should result in exercise becoming part of all late-onset Pompe disease patients treatment and lifestyle.
Practical advice
In addition to the need of greater sample size and a wider research base, there a few further considerations. The training program could be experimented with to increase the diversity of training methods. Progression ceased after the first 3 weeks, in line with progressive overload training loads (however modest) should continue to test participants. In addition, this study makes no reference to participant diet. This could perhaps explain no changes in body composition.
Further information/resources
The Pompe Community is a very useful tool and support network that can be utilised by people suffering from this disease.
The National Organization for Rare Disorders (NORD) is a similarly helpful resource that provides a range of information and ways to get in touch with experts in the field.
References
1. Di Iorio, G., Cipullo, F., Stromillo, L., Sodano, L., Capone, E., & Farina, O. (2011). S1.3 Adult-onset Pompe disease. Acta Myologica, 30(3), 200–202.
2. Kazi, Z. B., Prater, S. N., Kobori, J. A., Viskochil, D., Bailey, C., Gera, R., … Kishnani, P. S. (2016). Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses. JCI Insight, 1(11), e86821. http://doi.org/10.1172/jci.insight.86821
3. A.E. Slonim, L. Bulone, T. Goldberg, J. Mikekes, E. Slonim, J. Galanko, F. Martiniuk Modification of the natural history of adult-onset acid maltase deficiency by nutrition and exercise therapy Muscle Nerve, 35 (2007), pp. 70–77
4. Terzis, G., Dimopoulos, F., Papadimas, G. K., Papadopoulos, C., Spengos, K., Fatouros, I., ... & Manta, P. (2011). Effect of aerobic and resistance exercise training on late-onset Pompe disease patients receiving enzyme replacement therapy. Molecular genetics and metabolism, 104(3), 279-283.