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

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  • Mathula Thangarajh
  • Aiping Zhang
  • Kirandeep Gill
  • Habtom W Ressom
  • Zhenzhi Li
  • Rency S Varghese
  • Eric P Hoffman
  • Kanneboyina Nagaraju
  • Yetrib Hathout
  • Simina M Boca

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

Suggested Citation

  • Mathula Thangarajh & Aiping Zhang & Kirandeep Gill & Habtom W Ressom & Zhenzhi Li & Rency S Varghese & Eric P Hoffman & Kanneboyina Nagaraju & Yetrib Hathout & Simina M Boca, 2019. "Discovery of potential urine-accessible metabolite biomarkers associated with muscle disease and corticosteroid response in the mdx mouse model for Duchenne," PLOS ONE, Public Library of Science, vol. 14(7), pages 1-17, July.
    • Handle: RePEc:plo:pone00:0219507
    DOI: 10.1371/journal.pone.0219507
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    1. Layal Antoury & Ningyan Hu & Leonora Balaj & Sudeshna Das & Sofia Georghiou & Basil Darras & Tim Clark & Xandra O. Breakefield & Thurman M. Wheeler, 2018. "Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. John D. Storey, 2002. "A direct approach to false discovery rates," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 64(3), pages 479-498, August.
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