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Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

Lookup NU author(s): Dr Alison Blain, Professor Hanns Lochmuller



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


There is currently an urgent need for biomarkers that can be used to monitor the efficacy of experimental therapies for Duchenne Muscular Dystrophy (DMD) in clinical trials. Identification of novel protein biomarkers has been limited due to the massive complexity of the serum proteome and the presence of a small number of very highly abundant proteins. Here we have utilised an aptamer-based proteomics approach to profile 1,129 proteins in the serum of wild-type and mdx (dystrophin deficient) mice. The serum levels of 96 proteins were found to be significantly altered (P < 0.001, q < 0.01) in mdx mice. Additionally, systemic treatment with a peptide-antisense oligonucleotide conjugate designed to induce Dmd exon skipping and recover dystrophin protein expression caused many of the differentially abundant serum proteins to be restored towards wild-type levels. Results for five leading candidate protein biomarkers (Pgam1, Tnni3, Camk2b, Cycs and Adamts5) were validated by ELISA in the mouse samples. Furthermore, ADAMTS5 was found to be significantly elevated in human DMD patient serum. This study has identified multiple novel, therapy-responsive protein biomarkers in the serum of the mdx mouse with potential utility in DMD patients.

Publication metadata

Author(s): Coenen-Stass AML, McClorey G, Manzano R, Betts CA, Blain A, Saleh AF, Gait MJ, Lochmuller H, Wood MJA, Roberts TC

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2015

Volume: 5

Pages: 1-10

Online publication date: 23/11/2015

Acceptance date: 22/10/2015

Date deposited: 07/01/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/srep17014


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Funder referenceFunder name
U105178803Medical Research Council (MRC programme)
Medical Research Council Centre for Neuromuscular Diseases Biobank (Newcastle), EuroBioBank
Medical Research Council UK Centenary Early Career Award