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

Ingrid E C Verhaart,Kayleigh Putker,Annemieke Aartsma-Rus,Davy Van De Vijver,Kevin Adamzek,Maaike Van Putten,Joke W Boertje-Van Der Meulen,William D Phillips

doi:10.1371/journal.pone.0215335

Ingrid E C Verhaart, Kayleigh Putker + Show 6 more

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https://doi.org/10.1371/journal.pone.0215335

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Journal: PloS one	Publication Date: Apr 24, 2019
Citations: 3	License type: CC BY 4.0

Affiliation: Leiden University Medical Center

Abstract

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.

Highlights

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder, affecting around 1 in 5 000 newborn boys [1]
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
To direct effects of lack of dystrophin on muscle damage, many secondary consequences, like disturbances in muscle metabolism are seen in DMD patients [5]

Summary

Introduction

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. 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]

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