Research Article: A modified diet does not ameliorate muscle pathology in a mouse model for Duchenne muscular dystrophy

Date Published: April 24, 2019

Publisher: Public Library of Science

Author(s): Ingrid E. C. Verhaart, Davy van de Vijver, Joke W. Boertje-van der Meulen, Kayleigh Putker, Kevin Adamzek, Annemieke Aartsma-Rus, Maaike van Putten, William D Phillips.


Duchenne muscular dystrophy (DMD) is caused by a lack of dystrophin protein. Next to direct effects on the muscles, this has also metabolic consequences. The influence of nutrition on disease progression becomes more and more recognized. Protein intake by DMD patients may be insufficient to meet the increased demand of the constantly regenerating muscle fibers. This led to the hypothesis that improving protein uptake by the muscles could have therapeutic effects. The present study examined the effects of a modified diet, which composition might stimulate muscle growth, on disease pathology in the D2-mdx mouse model. D2-mdx males were fed with either a control diet or modified diet, containing high amounts of branched-chain amino acids, vitamin D3 and ursolic acid, for six weeks. Our study indicates that the modified diet could not ameliorate the muscle pathology. No effects on bodyweight or weight of individual muscles were observed. Neither did the diet affect severity of fibrosis or calcification of the muscles.

Partial Text

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder, affecting around 1 in 5 000 newborn boys [1]. First symptoms become apparent at approximately 2–3 years of age, whereupon muscle function gradually declines. Consequently, patients become wheelchair dependent around 10-12 years of age, followed by respiratory and cardiac failure, eventually leading to death around 30 years of age [2, 3]. DMD is caused by mutations in the DMD gene encoding for the dystrophin protein. Dystrophin plays an important role in stabilizing the muscle fibers and protecting them against damage during contractions. Its absence causes continues cycles of muscle degeneration and regeneration, eventually leading to the replacement of muscle tissue by adipose and fibrotic tissue [4].

Since protein supply may be insufficient in DMD and could exacerbate pathology, the effect of a modified diet on dystrophic pathology was examined in D2-mdx males. After determining caloric intake for one week, mice (aged six weeks) were randomized into two groups and fed with either a modified diet, rich in BCAA, vitamin D3 and ursolic acid (n = 8), or a control diet (RM3 chow) (n = 7) for a duration of six weeks. All mice were included in the analyses.

Next to direct effects of lack of dystrophin on muscle damage, many secondary consequences, like disturbances in muscle metabolism are seen in DMD patients [5]. The continuous muscle damage leads to increased degeneration and regeneration, which also impacts energy, especially protein, demands. Insufficient protein supply may therefore exaggerate muscle pathology. For BL10-mdx mice it is known that, especially in young mice, protein demand is very high due to rapid protein turnover and muscle hypertrophy [7]. It is not known whether this is also the case for D2-mdx mice as this model has not fully been characterized yet [34].