Recent progress in elucidating mechanisms underlying muscular dystrophy and muscle disease has dramatically increased the number of potentially druggable targets available for therapeutic intervention. Concurrently, hew approaches have increased the number of compounds that can be tested for activity against these targets. Together, these trends have stimulated the adoption of high-throughput screening (HTS) as a primary tool for early-stage drug discovery. HTS has already been applied to a limited set of muscular dystrophy targets, leading to therapeutics currently being tested in the clinic. This has increased enthusiasm worldwide and among CDMD Investigators for designing and implementing muscular dystrophy relevant HTS assays for drug discovery and elucidation of basic aspects of muscle cell biology. UCLA has already made a tremendous commitment to HTS screening on campus through the Molecular Shared Screening Resource (MSSR) to facilitate translational medicine, in general. Core B extends this set of resources to facilitate the screening of muscle/dystrophy relevant targets by providing manpower, cell models, expertise, eqiuipment and space for cell reprogramming, expansion and banking to support muscle centric projects. A major focus of the core is developing and distributing human patient cell based dystrophy models, including iDRM.(induced directly reprogrammable myotubes) and IPSC (induced pleurepotent stem cells), from patients with Duchenne and other dystrophies for use in HTS and validation of target hits and other interventions. Thus, the core maximizes impact by leveraging the existing UCLA investment in HTS technology by providing the needed resources and skills to "fill the gaps" to make muscle/dystrophy relevant assays readily and simply feasible on campus for center members.
Aim 1) To advise and assist users in muscle centric HTS assay development, application and data analysis in collaboration with the MSSR;
Aim 2) To develop, validate expand, bank and distibute primary/reprogrammed cells derived from Duchenne and other dystrophy patients;
Aim 3) To provide support, expertise, equipment and BSL2+ cuture space for utilization of developed cell based models for drug/therapy/target validation.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
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Special Emphasis Panel (ZAR1-XZ (M1))
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University of California Los Angeles
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Villalta, S Armando; Rosenthal, Wendy; Martinez, Leonel et al. (2014) Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. Sci Transl Med 6:258ra142
Ermolova, N V; Martinez, L; Vetrone, S A et al. (2014) Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function. Neuromuscul Disord 24:583-95
Swaggart, Kayleigh A; Demonbreun, Alexis R; Vo, Andy H et al. (2014) Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair. Proc Natl Acad Sci U S A 111:6004-9
Nelson, Michael D; Rader, Florian; Tang, Xiu et al. (2014) PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085-91
Lee, Hane; Deignan, Joshua L; Dorrani, Naghmeh et al. (2014) Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 312:1880-7
Sareen, Dhruv; O'Rourke, Jacqueline G; Meera, Pratap et al. (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med 5:208ra149
Rudnik-Schoneborn, Sabine; Senderek, Jan; Jen, Joanna C et al. (2013) Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. Neurology 80:438-46
Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J et al. (2013) The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy. FEBS J 280:4210-29
Wan, Jijun; Yourshaw, Michael; Mamsa, Hafsa et al. (2012) Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat Genet 44:704-8
Kudryashova, Elena; Kramerova, Irina; Spencer, Melissa J (2012) Satellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H. J Clin Invest 122:1764-76

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