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Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay
Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression it is important to know the natural variation of dystrophin expression between different muscles and...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971009/ https://www.ncbi.nlm.nih.gov/pubmed/33723284 http://dx.doi.org/10.1038/s41598-021-84863-w |
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author | Koeks, Z. Janson, A. A. Beekman, C. Signorelli, M. van Duyvenvoorde, H. A. van den Bergen, J. C. Hooijmans, M. T. Alleman, I. Hegeman, I. M. Verschuuren, J. J. G. M. v. Deutekom, J. C. Spitali, P. Datson, N. A. Niks, E. H. |
author_facet | Koeks, Z. Janson, A. A. Beekman, C. Signorelli, M. van Duyvenvoorde, H. A. van den Bergen, J. C. Hooijmans, M. T. Alleman, I. Hegeman, I. M. Verschuuren, J. J. G. M. v. Deutekom, J. C. Spitali, P. Datson, N. A. Niks, E. H. |
author_sort | Koeks, Z. |
collection | PubMed |
description | Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression it is important to know the natural variation of dystrophin expression between different muscles and over time. Dystrophin was quantified using capillary Western immunoassay (Wes) in the anterior tibial (TA) muscle of 37 BMD patients. Variability was studied using two samples from the same TA biopsy site in nine patients, assessing nine longitudinal TA biopsies, and eight simultaneously obtained vastus lateralis (VL) muscle biopsies. Measurements were performed in duplicate with two primary antibodies. Baseline dystrophin levels were correlated to longitudinal muscle strength and functional outcomes. Results showed low technical variability and high precision for both antibodies. Dystrophin TA levels ranged from 4.8 to 97.7%, remained stable over a 3–5 year period, and did not correlate with changes in longitudinal muscle function. Dystrophin levels were comparable between TA and VL muscles. Intra-muscle biopsy variability was low (5.2% and 11.4% of the total variability of the two antibodies). These observations are relevant for the design of clinical trials targeting dystrophin production, and may urge the need for other biomarkers or surrogate endpoints. |
format | Online Article Text |
id | pubmed-7971009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79710092021-03-19 Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay Koeks, Z. Janson, A. A. Beekman, C. Signorelli, M. van Duyvenvoorde, H. A. van den Bergen, J. C. Hooijmans, M. T. Alleman, I. Hegeman, I. M. Verschuuren, J. J. G. M. v. Deutekom, J. C. Spitali, P. Datson, N. A. Niks, E. H. Sci Rep Article Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression it is important to know the natural variation of dystrophin expression between different muscles and over time. Dystrophin was quantified using capillary Western immunoassay (Wes) in the anterior tibial (TA) muscle of 37 BMD patients. Variability was studied using two samples from the same TA biopsy site in nine patients, assessing nine longitudinal TA biopsies, and eight simultaneously obtained vastus lateralis (VL) muscle biopsies. Measurements were performed in duplicate with two primary antibodies. Baseline dystrophin levels were correlated to longitudinal muscle strength and functional outcomes. Results showed low technical variability and high precision for both antibodies. Dystrophin TA levels ranged from 4.8 to 97.7%, remained stable over a 3–5 year period, and did not correlate with changes in longitudinal muscle function. Dystrophin levels were comparable between TA and VL muscles. Intra-muscle biopsy variability was low (5.2% and 11.4% of the total variability of the two antibodies). These observations are relevant for the design of clinical trials targeting dystrophin production, and may urge the need for other biomarkers or surrogate endpoints. Nature Publishing Group UK 2021-03-15 /pmc/articles/PMC7971009/ /pubmed/33723284 http://dx.doi.org/10.1038/s41598-021-84863-w Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Koeks, Z. Janson, A. A. Beekman, C. Signorelli, M. van Duyvenvoorde, H. A. van den Bergen, J. C. Hooijmans, M. T. Alleman, I. Hegeman, I. M. Verschuuren, J. J. G. M. v. Deutekom, J. C. Spitali, P. Datson, N. A. Niks, E. H. Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay |
title | Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay |
title_full | Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay |
title_fullStr | Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay |
title_full_unstemmed | Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay |
title_short | Low dystrophin variability between muscles and stable expression over time in Becker muscular dystrophy using capillary Western immunoassay |
title_sort | low dystrophin variability between muscles and stable expression over time in becker muscular dystrophy using capillary western immunoassay |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971009/ https://www.ncbi.nlm.nih.gov/pubmed/33723284 http://dx.doi.org/10.1038/s41598-021-84863-w |
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