Identification of serum protein biomarkers for utrophin based DMD therapy.

Despite promising therapeutic avenues, there is currently no effective treatment for Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by the loss of the large cytoskeletal protein, dystrophin. A highly promising approach to therapy, applicable to all DMD patients irrespective to...

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Main Authors: Guiraud, S, Edwards, B, Squire, S, Babbs, A, Shah, N, Berg, A, Chen, H, Davies, K
Format: Journal article
Language:English
Published: Nature Publishing Group 2017
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author Guiraud, S
Edwards, B
Squire, S
Babbs, A
Shah, N
Berg, A
Chen, H
Davies, K
author_facet Guiraud, S
Edwards, B
Squire, S
Babbs, A
Shah, N
Berg, A
Chen, H
Davies, K
author_sort Guiraud, S
collection OXFORD
description Despite promising therapeutic avenues, there is currently no effective treatment for Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by the loss of the large cytoskeletal protein, dystrophin. A highly promising approach to therapy, applicable to all DMD patients irrespective to their genetic defect, is to modulate utrophin, a functional paralogue of dystrophin, able to compensate for the primary defects of DMD restoring sarcolemmal stability. One of the major difficulties in assessing the effectiveness of therapeutic strategies is to define appropriate outcome measures. In the present study, we utilised an aptamer based proteomics approach to profile 1,310 proteins in plasma of wild-type, mdx and Fiona (mdx overexpressing utrophin) mice. Comparison of the C57 and mdx sera revealed 83 proteins with statistically significant >2 fold changes in dystrophic serum abundance. A large majority of previously described biomarkers (ANP32B, THBS4, CAMK2A/B/D, CYCS, CAPNI) were normalised towards wild-type levels in Fiona animals. This work also identified potential mdx markers specific to increased utrophin (DUS3, TPI1) and highlights novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1). We define a panel of putative protein mdx biomarkers to evaluate utrophin based strategies which may help to accelerate their translation to the clinic.
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spelling oxford-uuid:2da413ed-0eca-44be-ab5f-bb8fce77fe772022-03-26T12:44:12ZIdentification of serum protein biomarkers for utrophin based DMD therapy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2da413ed-0eca-44be-ab5f-bb8fce77fe77EnglishSymplectic Elements at OxfordNature Publishing Group2017Guiraud, SEdwards, BSquire, SBabbs, AShah, NBerg, AChen, HDavies, KDespite promising therapeutic avenues, there is currently no effective treatment for Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by the loss of the large cytoskeletal protein, dystrophin. A highly promising approach to therapy, applicable to all DMD patients irrespective to their genetic defect, is to modulate utrophin, a functional paralogue of dystrophin, able to compensate for the primary defects of DMD restoring sarcolemmal stability. One of the major difficulties in assessing the effectiveness of therapeutic strategies is to define appropriate outcome measures. In the present study, we utilised an aptamer based proteomics approach to profile 1,310 proteins in plasma of wild-type, mdx and Fiona (mdx overexpressing utrophin) mice. Comparison of the C57 and mdx sera revealed 83 proteins with statistically significant >2 fold changes in dystrophic serum abundance. A large majority of previously described biomarkers (ANP32B, THBS4, CAMK2A/B/D, CYCS, CAPNI) were normalised towards wild-type levels in Fiona animals. This work also identified potential mdx markers specific to increased utrophin (DUS3, TPI1) and highlights novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1). We define a panel of putative protein mdx biomarkers to evaluate utrophin based strategies which may help to accelerate their translation to the clinic.
spellingShingle Guiraud, S
Edwards, B
Squire, S
Babbs, A
Shah, N
Berg, A
Chen, H
Davies, K
Identification of serum protein biomarkers for utrophin based DMD therapy.
title Identification of serum protein biomarkers for utrophin based DMD therapy.
title_full Identification of serum protein biomarkers for utrophin based DMD therapy.
title_fullStr Identification of serum protein biomarkers for utrophin based DMD therapy.
title_full_unstemmed Identification of serum protein biomarkers for utrophin based DMD therapy.
title_short Identification of serum protein biomarkers for utrophin based DMD therapy.
title_sort identification of serum protein biomarkers for utrophin based dmd therapy
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