Mass spectrometry-based protein analysis to unravel the tissue pathophysiology in Duchenne muscular dystrophy

2017 ◽  
Vol 12 (2) ◽  
pp. 1700071 ◽  
Author(s):  
Stephanie J. Carr ◽  
René P. Zahedi ◽  
Hanns Lochmüller ◽  
Andreas Roos
Keyword(s):  
Mass Spectrometry ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Protein Analysis

P1.49 Mass spectrometry based clinical proteomics for biomarker discovery in Duchenne muscular dystrophy

2011 ◽  
Vol 21 (9-10) ◽  
pp. 656
Author(s):  
F.C. Martin ◽  
S. Oonk ◽  
P.A.C. ’t Hoen ◽  
V.D. Nadarajah ◽  
A. Chaouch ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Biomarker Discovery ◽  
Clinical Proteomics

scholarly journals Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ivana Dabaj ◽  
Justine Ferey ◽  
Florent Marguet ◽  
Vianney Gilard ◽  
Carole Basset ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
High Resolution Mass Spectrometry ◽  
Phospholipid Metabolism ◽  
Ion Cyclotron Resonance ◽  
Unbiased Manner ◽  
Phosphatidic Acids ◽  
Muscle Biopsies

AbstractDuchenne muscular dystrophy (DMD) is a common and severe X-linked myopathy, characterized by muscle degeneration due to altered or absent dystrophin. DMD has no effective cure, and the underlying molecular mechanisms remain incompletely understood. The aim of this study is to investigate the metabolic changes in DMD using mass spectrometry-based imaging. Nine human muscle biopsies from DMD patients and nine muscle biopsies from control individuals were subjected to untargeted MSI using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry. Both univariate and pattern recognition techniques have been used for data analysis. This study revealed significant changes in 34 keys metabolites. Seven metabolites were decreased in the Duchenne biopsies compared to control biopsies including adenosine triphosphate, and glycerophosphocholine. The other 27 metabolites were increased in the Duchenne biopsies, including sphingomyelin, phosphatidylcholines, phosphatidic acids and phosphatidylserines. Most of these dysregulated metabolites are tightly related to energy and phospholipid metabolism. This study revealed a deep metabolic remodelling in phospholipids and energy metabolism in DMD. This systems-based approach enabled exploring the metabolism in DMD in an unprecedented holistic and unbiased manner with hypothesis-free strategies.

scholarly journals Exon-skipped dystrophins for treatment of Duchenne muscular dystrophy: Mass spectrometry mapping of most exons and cooperative domain designs based on single molecule mechanics

Cytoskeleton ◽  
2010 ◽  
Vol 67 (12) ◽  
pp. 796-807 ◽  
Author(s):  
Christine Carag Krieger ◽  
Nishant Bhasin ◽  
Manorama Tewari ◽  
Andre E. X. Brown ◽  
Daniel Safer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Single Molecule ◽  
Cooperative Domain

scholarly journals Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy

Gene Therapy ◽  
2021 ◽  
Author(s):  
Vahid Farrokhi ◽  
Jason Walsh ◽  
Joe Palandra ◽  
Joanne Brodfuehrer ◽  
Teresa Caiazzo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gene Therapy ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Biceps Femoris ◽  
Dystrophin Gene ◽  
Limit Of Quantification ◽  
Post Dose ◽  
Validation Data ◽  
Dystrophin Expression

AbstractDuchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of the protein dystrophin. Gene therapy strategies that aim to increase expression of a functional dystrophin protein (mini-dystrophin) are under investigation. The ability to accurately quantify dystrophin/mini-dystrophin is essential in assessing the level of gene transduction. We demonstrated the validation and application of a novel peptide immunoaffinity liquid chromatography–tandem mass spectrometry (IA-LC-MS/MS) assay. Data showed that dystrophin expression in Becker muscular dystrophy and DMD tissues, normalized against the mean of non-dystrophic control tissues (n = 20), was 4–84.5% (mean 32%, n = 20) and 0.4–24.1% (mean 5%, n = 20), respectively. In a DMD rat model, biceps femoris tissue from dystrophin-deficient rats treated with AAV9.hCK.Hopti-Dys3978.spA, an adeno-associated virus vector containing a mini-dystrophin transgene, showed a dose-dependent increase in mini-dystrophin expression at 6 months post-dose, exceeding wildtype dystrophin levels at high doses. Validation data showed that inter- and intra-assay precision were ≤20% (≤25% at the lower limit of quantification [LLOQ]) and inter- and intra-run relative error was within ±20% (±25% at LLOQ). IA-LC-MS/MS accurately quantifies dystrophin/mini-dystrophin in human and preclinical species with sufficient sensitivity for immediate application in preclinical/clinical trials.

Growth and psychomotor development of patients with Duchenne Muscular Dystrophy

2012 ◽  
Vol 43 (02) ◽  
Author(s):  
E Sarrazin ◽  
M von der Hagen ◽  
U Schara ◽  
K von Au ◽  
A Kaindl
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Psychomotor Development
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