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

被引：47

作者：

Coenen-Stass, Anna M. L. ^{[1
]}

McClorey, Graham ^{[1
]}

Manzano, Raquel ^{[1
]}

Betts, Corinne A. ^{[1
]}

Blain, Alison ^{[2
]}

Saleh, Amer F. ^{[3
]}

Gait, Michael J. ^{[3
]}

Lochmueller, Hanns ^{[2
]}

Wood, Matthew J. A. ^{[1
]}

Roberts, Thomas C. ^{[1
,4
]}

机构：

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England

[2] Newcastle Univ, Inst Med Genet, MRC, John Walton Muscular Dystrophy Res Ctr,Ctr Neurom, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[3] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

[4] Sanford Burnham Prebys Med Discovery Inst, Dev Aging & Regenerat Program, La Jolla, CA 92037 USA

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

英国医学研究理事会;

关键词：

CREATINE-KINASE; MDX MOUSE; MICRORNAS; DISCOVERY; MARKERS; MICE; DMD;

D O I：

10.1038/srep17014

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 40 条

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