title: Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study.
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.
authors.affiliation: Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, United States of America.|Department of Oncology, Georgetown University Medical Center, Washington, DC, United States of America.|Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Simina M
authors.identifier: http://orcid.org/0000-0002-1400-3398
authors.initials: SM
authors.lastname: Boca
authors.affiliation: Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Maki
authors.initials: M
authors.lastname: Nishida
authors.affiliation: Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Harris
authors.affiliation: Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Shruti
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, DC, United States of America.|Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Gill
authors.affiliation: Children's National Medical Center and the George Washington University, Washington, DC, United States of America.
authors.forename: Haeri
authors.initials: H
authors.lastname: Seol
authors.affiliation: Children's National Medical Center and the George Washington University, Washington, DC, United States of America.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Morgenroth
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of California Davis, School of Medicine, Davis, California, United States of America.
authors.forename: Erik
authors.initials: E
authors.lastname: Henricson
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of California Davis, School of Medicine, Davis, California, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Department of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Alberta, Canada.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Mah
authors.affiliation: Neurology Service, Department of Veteran Affairs Medical Center, Pittsburgh, Pennsylvania, United States of America.|Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Paula R
authors.initials: PR
authors.lastname: Clemens
authors.affiliation: Children's National Medical Center and the George Washington University, Washington, DC, United States of America.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Children's National Medical Center and the George Washington University, Washington, DC, United States of America.
authors.forename: Yetrib
authors.initials: Y
authors.lastname: Hathout
authors.affiliation: Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, United States of America.|Department of Oncology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Subha
authors.initials: S
authors.lastname: Madhavan
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D018450:Disease Progression; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers