Journal article
Duchenne and Becker Muscular Dystrophies: A Review of Animal Models, Clinical End Points, and Biomarker Quantification
Toxicologic pathology, Vol.45(7), pp.961-976
10/2017
DOI: 10.1177/0192623317734823
PMCID: PMC5788182
PMID: 28974147
Abstract
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are neuromuscular disorders that primarily affect boys due to an X-linked mutation in the DMD gene, resulting in reduced to near absence of dystrophin or expression of truncated forms of dystrophin. Some newer therapeutic interventions aim to increase sarcolemmal dystrophin expression, and accurate dystrophin quantification is critical for demonstrating pharmacodynamic relationships in preclinical studies and clinical trials. Current challenges with measuring dystrophin include the variation in protein expression within individual muscle fibers and across whole muscle samples, the presence of preexisting dystrophin-positive revertant fibers, and trace amounts of residual dystrophin. Immunofluorescence quantification of dystrophin can overcome many of these challenges, but manual quantification of protein expression may be complicated by variations in the collection of images, reproducible scoring of fluorescent intensity, and bias introduced by manual scoring of typically only a few high-power fields. This review highlights the pathology of DMD and BMD, discusses animal models of DMD and BMD, and describes dystrophin biomarker quantitation in DMD and BMD, with several image analysis approaches, including a new automated method that evaluates protein expression of individual muscle fibers.
Details
- Title: Subtitle
- Duchenne and Becker Muscular Dystrophies: A Review of Animal Models, Clinical End Points, and Biomarker Quantification
- Creators
- Kristin Wilson - 1 Flagship Biosciences, Inc., Westminster, Colorado, USACrystal Faelan - 1 Flagship Biosciences, Inc., Westminster, Colorado, USAJanet C Patterson-Kane - 1 Flagship Biosciences, Inc., Westminster, Colorado, USADaniel G Rudmann - 1 Flagship Biosciences, Inc., Westminster, Colorado, USASteven A Moore - 2 Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USADiane Frank - 3 Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USAJay Charleston - 3 Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USAJon Tinsley - 4 Summit Therapeutics, Abingdon, United KingdomG David Young - 1 Flagship Biosciences, Inc., Westminster, Colorado, USAAnthony J Milici - 1 Flagship Biosciences, Inc., Westminster, Colorado, USA
- Resource Type
- Journal article
- Publication Details
- Toxicologic pathology, Vol.45(7), pp.961-976
- Publisher
- United States
- DOI
- 10.1177/0192623317734823
- PMID
- 28974147
- PMCID
- PMC5788182
- ISSN
- 0192-6233
- eISSN
- 1533-1601
- Grant note
- U54 NS053672 / NINDS NIH HHS
- Language
- English
- Date published
- 10/2017
- Academic Unit
- Pathology
- Record Identifier
- 9984047742302771
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