# Exercise as it relates to Disease/The Benefits of Endurance Training in Adult Men with Becker Muscular Dystrophy

This Wikibooks page is a fact sheet and analysis of the paper “Endurance training improves fitness and strength in patients with Becker muscular dystrophy” by Sven et al. (2008) as part of an assignment for the University of Canberra.

## Background
### Becker Muscular Dystrophy Overview

Becker muscular dystrophy (BMD) is a degenerative genetic disorder linked to the x-chromosome. The disease occurs when there is a mutation to the dystrophin gene, which is required to make functional copies of the protein dystrophin. Dystrophin is believed to play an important structural role in linking the contractile filaments of the muscle to the extracellular matrix, which helps stabilise the cell membrane of muscles during contraction, which is needed to maintain muscle integrity. There are nine major types of muscular dystrophy. The genetic mutation that results in BMD results in some sufferers having some functional dystrophin as well as non-functional dystrophin. Due to the synthesis of some functional dystrophin, the severity of BMD symptoms is milder than other types of muscular dystrophy, such as Duchenne muscular dystrophy (DMD), sufferers of which nearly or completely lose the ability to create functional dystrophin. This loss in functional dystrophin generally effects skeletal muscles first, particularity in the lower body (hips and legs), resulting in weakened muscles and movement difficulty. The progression of the disease can lead to more serious complications when it effects the cardiac (heart) tissue.

### What Is the Background to This Research

Prior to the study by Sven et al. (2008), studies had only been conducted on genetically modified mice called mdx mice, which have a mutation causing cells to produce a non-functional dystrophin protein, which more closely replicates a DMD state. Previous studies in mdx mice suggested that physical activity may have adverse side effects for muscle integrity and function and it was from these studies, recommendations for BMD exercise prescription were set. Therefore, Sven et al. (2008) aimed to test BMD more specifically and in humans, as until this point no studies had be done to investigate the effects of aerobic training in BMD patients. Previous studies done in DMD patients suggested exercise may inflict structural damage to muscles cells with defective dystrohpin, which would lead to an acceleration of the disease. Without research specfically investigating the effects of aerobic exercise on BMD, these DMD findings were extrapolated to the BMD recommendations.

## Where Is The Research From

The study was conducted by researchers at The Copenhagen Muscle Research Centre and academic staff at the University of Copenhagen who have collectively published multiple peer reviewed studies on topics related to muscle pathologies and exercise, including further work on muscular dystrophy. This study was published in a peer reviewed journal, the Oxford University Press. The study was funded by The University of Copenhagen and a variety of independent research foundations, with no immediately identifiable conflicts of interest.

### What Kind Of Study Is It?

The study is a cohort study (also known as a prospective observational study), as it is following a group with a condition (BMD) compared to a group without the condition (apparently healthy population). Exercise is introduced and its effects over time are monitored and compared in the two populations. According to The Centre for Evidence-Based Medicine’s Levels Of Evidence For Clinical Studies, cohort studies are rated level 2b out of a possible 5 (where 1 =highest level of evidence and 5 = lowest level of evidence acceptable to use in a clinical study), indicating the research method is in the moderate to high range for measurement of validity.

## What Did The Research Involve?
### Subjects

The study included eleven men between 28 and 36 years old who had been clinically diagnosed with BMD and seven apparently healthy men between 31 and 41 years old.
For subjects to be eligible to take part in the study, they had to fit the criteria of sedentary lifestyle behaviours (therefore no exercise training with the exception of up to 2 physiotherapy sessions per week), and have no known medical conditions (other than muscular dystrophy in the BMD group).

### Method

The initial design of the experiment involved the participants completing a 12 week aerobic training program at home on a stationary cycle ergometer. The participants were instructed to complete a total of 50 moderate intensity training aerobic sessions, each 30 minutes in duration over the 12 weeks. The number of weekly sessions progressively increased throughout the 12 week period, the exercise intensity however remained at a constant pre-determined level of 65% VO$_2$max. Of the eleven BMD patients, six expressed interest in continuing the training. Therefore their training programs were extended to 12 months, meaning a total of 12 months of data was collected for these participants. The other 5 BMD participants elected not to continue due to personal reasons (such as busy schedules and inconvenience of travelling to testing facilities), and reportedly not due adverse effects or lack of progress.
Figure 1: Measures collected by researchers to monitor adherence, progress and safety
| Adherence | Progress | Safety |
| Pulse watch | Muscle strength (dynamometry) | Plasma CK measurement |
| Weekly telephone consultation | MSF-36 Questionnaire | Muscle biopsy |
| Training diary | DEXA scanning | Echocardiography |

## Results
### What were the important findings?

Following the 12 weeks of aerobic training the BMD patients saw an 47% increase in VO$_2$max, which was 3-fold greater increase in VO$_2$max than in the apparently healthy population. These improvements were noted to be maintained (but not increased) in the BMD participants who continued training until 12 months. The maximal workload of the BMD participants increased 80%, a 4-fold greater increase than in the healthy participants. Significant increases in lower body muscular strength were reported. Self reported activities of daily living also improved as reported on the MFS-36 Questionnaire, with particular improvements in walking distance. A major finding of this research related to the plasma CK levels which were measured weekly during the 12 week period, and monthly for the continuing group. The plasma CK levels remained unchanged throughout the training program, indicating no significant muscle damage was occurring. To further support this, none of the BMD or healthy participants reported any adverse effects to the training program.

### How did the researchers interpret the results?

The researchers believe that their study provides evidence that in humans, moderate intensity aerobic exercise is safe for sufferers of BMD, despite previous recommendations indicating exercise training may be deleterious for the progression of BMD disease. The researchers indicated that all precautions for safety and the detailed monitoring procedures for changes in participants condition, showed the training measurably improved the condition, or at least did not negatively effect (therefore no change in measure) their participants.

## What conclusions can we take from this research?

It is important to note that this study was not seeking to improve the BMD in the patients, however, was testing the safety and effectiveness of aerobic training on fitness in BMD patients compared to a healthy population. The results indicate that using the exercise protocol of 30 minutes cycling at an intensity of 65% VO$_2$max is a safe an effective method of enhancing endurance performance, the benefits of which could be observed in the participants activities of daily living. It is also important to highlight that this study was on 11 adult men, as the severity of BMD is on a spectrum, the results from 11 men aged 28 to 36 years cannot be generalised to BMD patients, as it can effect any age group.

### How do the findings align with other research in the area

In a meta-analysis of muscular dystrophy studies, Imelda et al. (2012) have also indicated that moderate intensity aerobic training appears to not be harmful in people with BMD and can have a positive effect on the functioning, activities and participation on patients. Further recommending that exercise prescription in this population should be individualised and in line with the American College of Sports Medicine's Position Stand (see further reading section for link). The meta-analysis also recommended that more studies in this field need to be done, as there number of high quality studies in this area is low.

## Further reading

BMD Factsheet: http://patient.info/doctor/beckers-muscular-dystrophy
Overview of Additional BMD Research Avenues: https://www.mda.org/disease/becker-muscular-dystrophy/research
American College of Sports Medicine Position Stand: http://www.mhhe.com/hper/nutrition/williams/student/appendix_i.pdf
American College of Sports Medicine's Exercise Prescription Guidelines for Muscular Dystrophy Patients: http://www.medscape.com/viewarticle/719871
Rehabilitation in Muscular Dystrophies: Changing Approach: http://www.intechopen.com/books/muscular-dystrophy/rehabilitation-in-muscular-dystrophy

## References

* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Marie Louise Sveen, Tina D. Jeppesen, Simon Hauerslev, Lars KØber, Thomas O. Krag and John Vissing. Endurance training improves fitness and strength in patients with Becker muscular dystrophy. Oxford University Press. 2008; 131: p. 2824-2831.
* 1 2 3 Derek J. Blake, Andrew Weir, Sarah E. Newey, Kay E. Davies. Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle. Physiological Reviews. 2002; 82(2): p. 291-293.
* 1 2 3 4 Muscular Dystrophy Association. Becker Muscular Dystrophy (BMD). [Online].; 2015 [cited 23 September 2016]. Available from: https://www.mda.org/disease/becker-muscular-dystrophy.
* ↑ Pedro Miura, Bernard J. Jasmin. Utrophin upregulation for treating Duchenne or Becker muscular dystrophy: how close are we?. Trends in Molecular Medicine. 2006; 12(3): p. 122-123.
* ↑ Sacco P, Jones DA, Dick JR, Vrbova G. Contractile properties and susceptibility to exercise induced damage of normal and mdx mouse tibialis anterior muscle. Clinical Science (London). 1992; 82(2): p. 227–236.
* ↑ Granchelli JA, Pollina C, Hudecki MS. Pre-clinical screening of drugs using the mdx mouse. Neuromuscular Disorders. 2000; 10(4): p. 235–239.
* ↑ PubFacts.com. Publications Authored by Marie Louise Sveen. [Online].; 2015 [cited 24 September 2016]. Available from: http://www.pubfacts.com/author/Marie+Louise+Sveen.
* ↑ PubFacts.com. Publications Authored by Tina D Jeppesen. [Online].; 2015 [cited 24 September 2016]. Available from: http://www.pubfacts.com/author/Tina+D+Jeppesen.
* ↑ PubFacts.com. Publications Authored by Lars KØber. [Online].; 2015 [cited 24 September 2016]. Available from: http://www.pubfacts.com/author/Lars+K%C3%B8ber.
* ↑ PubFacts.com. Publications Authored by Simon Hauerslev. [Online].; 2015 [cited 24 September 2016]. Available from http://www.pubfacts.com/author/Simon+Hauerslev.
* ↑ PubFacts.com. Publications Authored by Thomas O Krag. [Online].; 2016 [cited 24 September 2016]. Available from: http://www.pubfacts.com/author/Thomas+O+Krag.
* ↑ PubFacts.com. Publications Authored by John Vissing. [Online].; 2016 [cited 24 September 2016]. Available from: http://www.pubfacts.com/author/John+Vissing.
* ↑ Jeremy Howick, Iain Chalmers, Paul Glasziou, Trish Greenhalgh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob Phillips, and Hazel Thornton. The 2011 Oxford CEBM Evidence Levels of Evidence (Introductory Document). [Online].; 2011 [cited 24 September 2016]. Available from: http://www.cebm.net/index.aspx?o=5653.
* ↑ Abdul Qawee Rani, Teguh Haryo Sasongko, Sarina Sulong, David Bunyan, Abdul Razak Salmi, Bin Alwi Zilfalil, Masafumi Matsuo and Zabidi-Hussin. Mutation spectrum of dystrophin gene in Malaysian patients with Duchenne/Becker muscular dystrophy. Journal of Neurogenetics 2013; 27(1): p. 11–15.
* 1 2 Imelda J.M. de Groot, Nicoline B.M. Voet, Merel Jansen and Lenie van den Engel-Hoek. Rehabilitation in Muscular Dystrophies: Changing Approach, Muscular Dystrophy. [Online].; 2012. InTech, DOI: 10.5772/32629. [cited 25 September 2016]. Available from: http://www.intechopen.com/books/muscular-dystrophy/rehabilitation-in-muscular-dystrophy.