title: Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.
abstract: Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20012;
authors.forename: Yetrib
authors.initials: Y
authors.lastname: Hathout
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Edward
authors.initials: E
authors.lastname: Brody
authors.affiliation: Neurology Service, Department of Veteran Affairs Medical Center, Pittsburgh, PA 15240; University of Pittsburgh, Pittsburgh, PA 15213;
authors.forename: Paula R
authors.initials: PR
authors.lastname: Clemens
authors.affiliation: The Heart Center, Nationwide Children's Hospital, The Ohio State University, Columbus, OH 15213;
authors.forename: Linda
authors.initials: L
authors.lastname: Cripe
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Robert Kirk
authors.initials: RK
authors.lastname: DeLisle
authors.affiliation: Parent Project Muscular Dystrophy, Hackensack, NJ 07601;
authors.forename: Pat
authors.initials: P
authors.lastname: Furlong
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20012;
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20012;
authors.forename: Lauren
authors.initials: L
authors.lastname: Hache
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of California Davis School of Medicine, Davis, CA 95618;
authors.forename: Erik
authors.initials: E
authors.lastname: Henricson
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20012;
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202;
authors.forename: Yvonne Monique
authors.initials: YM
authors.lastname: Kobayashi
authors.affiliation: The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;
authors.forename: Angela
authors.initials: A
authors.lastname: Lorts
authors.affiliation: Department of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, AB, Canada T3B 6A8;
authors.forename: Jean K
authors.initials: JK
authors.lastname: Mah
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of California Davis School of Medicine, Davis, CA 95618;
authors.forename: Craig
authors.initials: C
authors.lastname: McDonald
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Bob
authors.initials: B
authors.lastname: Mehler
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045;
authors.forename: Sally
authors.initials: S
authors.lastname: Nelson
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Malti
authors.initials: M
authors.lastname: Nikrad
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Britta
authors.initials: B
authors.lastname: Singer
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Fintan
authors.initials: F
authors.lastname: Steele
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: David
authors.initials: D
authors.lastname: Sterling
authors.affiliation: Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301;
authors.forename: Steve
authors.initials: S
authors.lastname: Williams
authors.affiliation: SomaLogic, Inc., Boulder, CO 80301; lgold@somalogic.com.
authors.forename: Larry
authors.initials: L
authors.lastname: Gold
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: SOMAmer; SOMAscan; biomarkers; muscular dystrophy; proteomics