Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study

Simina M. Boca, Maki Nishida, Michael Harris, Shruti Rao, Amrita K. Cheema, Kirandeep Gill, Haeri Seol, Lauren P. Morgenroth, Erik Henricson, Craig McDonald, Jean K. Mah, Paula R. Clemens, Eric P. Hoffman, Yetrib Hathout, Subha Madhavan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.

Original languageEnglish (US)
Pages (from-to)e0153461
JournalPLoS One
Volume11
Issue number4
DOIs
StatePublished - 2016

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Boca, S. M., Nishida, M., Harris, M., Rao, S., Cheema, A. K., Gill, K., Seol, H., Morgenroth, L. P., Henricson, E., McDonald, C., Mah, J. K., Clemens, P. R., Hoffman, E. P., Hathout, Y., & Madhavan, S. (2016). Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study. PLoS One, 11(4), e0153461. https://doi.org/10.1371/journal.pone.0153461