Project description:Antibody suspension bead array based profiling of plasma samples collected from Duchenne and Becker muscular dystrophy patients and non-diseased controls and carriers at 4 different clinical sites
Project description:Duchenne muscular dystrophy is caused by genetic defects in the gene encoding dystrophin and leads to progressive muscle degeneration. Glucocorticoid steroids are current mainstay pharmacological regimen to decrease muscle inflammation and prolong the ambulatory period in these patients, but daily intake of glucocorticoids like prednisone and deflazacort causes adverse side effects like osteoporosis, adrenal suppression, insulin resistance and obesity. Intermittent steroid dosing has been proposed as alternative to maintain benefits and limit side effects, but a detailed understanding of the mechanisms underpinning the regimen-specific effects in muscle is still missing. Here we explore how once-daily versus once-weekly prednisone (4 week-long treatment) affect the metabolomic landscape in mdx mouse muscle (genetic model of Duchenne muscular dystrophy; DBA/2J background) through metabolomics profiling.
Project description:Large animal models for Duchenne muscular dystrophy (DMD) are indispensible for preclinical evaluation of novel diagnostic procedures and treatment strategies. To evaluate functional consequences of Duchenne muscular dystrophy (DMD) in skeletal muscle and myocardium, we used a new genetically engineered dystrophin KO pig model displaying hallmarks of human DMD. Heart and skeletal muscle tissue samples of DMD pigs and wild-type (WT) controls at three different ages were analyzed by label-free proteomics.
Project description:Duchenne muscular dystrophy is caused by genetic defects in the gene encoding dystrophin and leads to progressive muscle degeneration. Glucocorticoid steroids are current mainstay pharmacological regimen to decrease muscle inflammation and prolong the ambulatory period in these patients, but daily intake of glucocorticoids like prednisone and deflazacort causes adverse side effects like osteoporosis, adrenal suppression, insulin resistance and obesity. Intermittent steroid dosing has been proposed as alternative to maintain benefits and limit side effects, but a detailed understanding of the mechanisms underpinning the regimen-specific effects in muscle is still missing. Here we explore how once-daily versus once-weekly prednisone (4 week-long treatment) affect the epigenomic landscape in mdx mouse muscle (genetic model of Duchenne muscular dystrophy; DBA/2J background) through H3K27 acetylation profiles.
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q. By comparing genome-wide gene expression data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders, we intend to identify disease-specific changes which are more likely to be involved in the early stages of the disease progression. The data will help to identify pathological mechanisms involved in FSHD. Experiment Overall Design: Comparison of the profiles of FSHD to 13 other conditions for disease-specific changes. The 13 conditions are NHM (Normal healthy muscle) n=15; JDM (Juvenile dermatomyositis) n=25; HSP (Human spastic paraplegia) n=4; FSHD (facioscapulohumeral dystrophy) unaffected n=5, affected n=9; FKRP (Fukutin related protein deficiency) n=7; ED-L (Emery-Dreifuss muscular dystrophy, lamin A/C deficiency) n=4; ED-E (Emery-Dreifuss muscular dystrophy, emerin deficiency) n=4; DYSF (dysferlinopathy) n=10; DMD (Duchenne Muscular Dystrophy) n=10; CALP (Calpain-3 deficiency) n=10; BMD (Becker Muscular Dystrophy) n=5; AQM (Acute quadriplegic myopathy) n=5; ALS (Amyotrophic lateral sclerosis) n=9.