Activities per year
Abstract
Objective: We formed a multi-institution collaboration in order to compare dystrophin quantification methods, reach a consensus on the most reliable method, and report its biological significance in the context of clinical trials. Methods: Five laboratories with expertise in dystrophin quantification performed a data-driven comparative analysis of a single reference set of normal and dystrophinopathy muscle biopsies using quantitative immunohistochemistry and Western blotting. We developed standardized protocols and assessed inter- and intralaboratory variability over a wide range of dystrophin expression levels. Results: Results from the different laboratories were highly concordant with minimal inter- and intralaboratory variability, particularly with quantitative immunohistochemistry. There was a good level of agreement between data generated by immunohistochemistry and Western blotting, although immunohistochemistry was more sensitive. Furthermore, mean dystrophin levels determined by alternative quantitative immunohistochemistry methods were highly comparable. Conclusions: Considering the biological function of dystrophin at the sarcolemma, our data indicate that the combined use of quantitative immunohistochemistry and Western blotting are reliable biochemical outcome measures for Duchenne muscular dystrophy clinical trials, and that standardized protocols can be comparable between competent laboratories. The methodology validated in our study will facilitate the development of experimental therapies focused on dystrophin production and their regulatory approval.
Original language | English |
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Pages (from-to) | 2062-2069 |
Number of pages | 8 |
Journal | Neurology |
Volume | 83 |
Issue number | 22 |
Early online date | 29 Oct 2014 |
DOIs | |
Publication status | Published - 25 Nov 2014 |
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Dive into the research topics of 'Dystrophin quantification: biological and translational research implications'. Together they form a unique fingerprint.Profiles
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Professor Karen Anthony
- University of Northampton, Science - Professor of Molecular Medicine
- Centre for Physical Activity and Life Sciences
- Northamptonshire Dementia Research & Innovation Centre
Person: Academic
Impacts
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FDA approves first drug to treat Duchenne muscular dystrophy (DMD)
Anthony, K. (Co-Investigator)
Impact: Public policy impacts, Health and Well-Being impacts, Quality of life impacts, 03: Good Health and Well-Being (UN SDG)
Activities
- 1 Participating in a conference or workshop
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Final COST Action meeting
Anthony, K. (Participant)
22 Mar 2017Activity: Organising a conference or workshop › Participating in a conference or workshop › Research