Discovery of potential urine-accessible metabolite biomarkers associated with muscle disease and corticosteroid response in the mdx mouse model for Duchenne

5Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

Abstract

Urine is increasingly being considered as a source of biomarker development in Duchenne Muscular Dystrophy (DMD), a severe, life-limiting disorder that affects approximately 1 in 4500 boys. In this study, we considered the mdx mice—a murine model of DMD—to discover biomarkers of disease, as well as pharmacodynamic biomarkers responsive to prednisolone, a corticosteroid commonly used to treat DMD. Longitudinal urine samples were analyzed from male age-matched mdx and wild-type mice randomized to prednisolone or vehicle control via liquid chromatography tandem mass spectrometry. A large number of metabolites (869 out of 6,334) were found to be significantly different between mdx and wild-type mice at baseline (Bonferroni-adjusted p-value < 0.05), thus being associated with disease status. These included a metabolite with m/z = 357 and creatine, which were also reported in a previous human study looking at serum. Novel observations in this study included peaks identified as biliverdin and hypusine. These four metabolites were significantly higher at baseline in the urine of mdx mice compared to wild-type, and significantly changed their levels over time after baseline. Creatine and biliverdin levels were also different between treated and control groups, but for creatine this may have been driven by an imbalance at baseline. In conclusion, our study reports a number of biomarkers, both known and novel, which may be related to either the mechanisms of muscle injury in DMD or prednisolone treatment.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Thangarajh, M., Zhang, A., Gill, K., Ressom, H. W., Li, Z., Varghese, R. S., … Boca, S. M. (2019). Discovery of potential urine-accessible metabolite biomarkers associated with muscle disease and corticosteroid response in the mdx mouse model for Duchenne. PLoS ONE, 14(7). https://doi.org/10.1371/journal.pone.0219507

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 8

57%

Researcher 5

36%

Professor / Associate Prof. 1

7%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 5

42%

Medicine and Dentistry 3

25%

Pharmacology, Toxicology and Pharmaceut... 2

17%

Agricultural and Biological Sciences 2

17%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 21

Save time finding and organizing research with Mendeley

Sign up for free