Core C will provide centralized and curated molecular diagnostics services, cell banking and distribution functions. All three projects rely on precise and accurate definition of the deletion mutations in each of the dystrophinopathy patients under study. The recruitment of all human subjects will be through the existing Cooperative International Neuromuscular Research Group (CINRG), with an established Coordinating Center (at Children's National Medical Center), elected Executive Committee, and 24 clinical recruitment sites. The CINRG group has an ongoing federally funded natural history study of 348 Duchenne muscular dystrophy patients, and multiple ongoing additional natural history studies and clinical trials of Duchenne/Becker muscular dystrophy and limb-girdle muscular dystrophy patients. Dystrophinopathy patient samples will be received from two distinct IRB protocols. For Duchenne muscular dystrophy participants (out-of-frame mutations). Core C will originate a protocol for receipt of blood (DNA) and skin biopsies (Aim 1). The Core will establish fibroblast cultures, validate and refine the deletion mutations using arrays and nextgen sequencing, and then distribute cells to Project 2. In the second human subject protocol. Project 3 will originate the protocol for a Becker muscular dystrophy natural history study (In-frame mutations), and collect blood (DNA), skin biopsy, and optional muscle biopsy specimens from each participant in the clinical study. All participant samples will be received and banked by Core C. DNA samples from both Duchenne and Becker muscular dystrophy patients will be tested for validation and refinement of the deletion mutations/breakpoints. Skin biopsies will be cultured for fibroblasts and cell cultures sent to Projects 1 and 2 and banked. Muscle biopsies will be sent to Project 1. Innovation is through novel methods of Identification of deletion breakpoints, and application of nextgen sequencing methods (Pacific Biosciences, lllumina). Resource sharing will include entry of alt patient mutation data Into existing International databases (Leiden Muscular Dystrophy Pages;TREAT-NMD Registry). The Core will send fibroblast cultures to external Investigators upon request. The Core will also be available for application of Innovative molecular diagnostics technologies to external investigators on a collaborative basis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR060836-03
Application #
8544779
Study Section
Special Emphasis Panel (ZAR1-KM)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$268,717
Indirect Cost
$77,708
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
Sreetama, S C; Takano, T; Nedergaard, M et al. (2016) Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis. Cell Death Differ 23:596-607
Hathout, Yetrib; Seol, Haeri; Han, Meng Hsuan J et al. (2016) Clinical utility of serum biomarkers in Duchenne muscular dystrophy. Clin Proteomics 13:9
Coley, William D; Bogdanik, Laurent; Vila, Maria Candida et al. (2016) Effect of genetic background on the dystrophic phenotype in mdx mice. Hum Mol Genet 25:130-45
Boca, Simina M; Nishida, Maki; Harris, Michael et al. (2016) Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study. PLoS One 11:e0153461
Hathout, Yetrib; Conklin, Laurie S; Seol, Haeri et al. (2016) Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children. Sci Rep 6:31727
Loell, Ingela; Raouf, Joan; Chen, Yi-Wen et al. (2016) Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents. Arthritis Res Ther 18:136
Dillingham, Blythe C; Benny Klimek, Margaret E; Gernapudi, Ramkishore et al. (2015) Inhibition of inflammation with celastrol fails to improve muscle function in dysferlin-deficient A/J mice. J Neurol Sci 356:157-62
Hathout, Yetrib; Brody, Edward; Clemens, Paula R et al. (2015) Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy. Proc Natl Acad Sci U S A 112:7153-8
Freishtat, R J; Nino, G; Tsegaye, Y et al. (2015) Pharmacologically-induced mitotic synchrony in airway epithelial cells as a mechanism of action of anti-inflammatory drugs. Respir Res 16:132
Echigoya, Yusuke; Aoki, Yoshitsugu; Miskew, Bailey et al. (2015) Long-term efficacy of systemic multiexon skipping targeting dystrophin exons 45-55 with a cocktail of vivo-morpholinos in mdx52 mice. Mol Ther Nucleic Acids 4:e225

Showing the most recent 10 out of 33 publications