Recent progress in elucidating the mechanisms underlying muscular dystrophy and muscle disease has dramatically increased the number of protein targets available for potential drug treatment. Concurrently, new 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. While HTS has only been applied to a limited set of muscular dystrophy targets, early application of this approach has already lead to the development of therapeutics currently being tested in the clinic. This has lead to increased enthusiasm worldwide and among UCLA MDTRaC Investigators for designing and implementing muscular dystrophy relevant assays for drug discovery. UCLA has already made a tremendous commitment to HTS screening on campus in the form of the UCLA MSSR as one mechanism by which to facilitate translational medicine, in general. However, access to this resource is currently limited by available manpower, cell models, expertise and space for cell expansion and handling of muscle lineage and muscular dystrophy relevant cells. To address this limitation we propose to create a muscle relevant HTS Core that will utilize the robotics and imaging capabilities of the MSSR and will provide manpower, expertise, space, resources, and guidance on muscle cell and fibroblast culture. In this context the HTS Assay Core will:
Aim 1) advise users in assay development and provide access to available muscle and muscular dystrophy relevant cell models;
Aim 2) provide cell culture expansion and plating (in HTS format) and MSSR interfacing services, Aim 3) retrieve and analyze and mine data collected at the MSSR;
and Aim 4) aid in development and implementation of secondary assays for lead hit compound validation. Thus, the proposed core maximizes impact by leveraging the existing tremendous investment in HTS technology already available on campus and implementing the needed resources and skills to """"""""fill the gaps"""""""" to make muscle and muscularly dystrophy relevant assays readily and simply feasible on campus for the center members.
Development and implementation of muscle/muscular dystrophy relevant high throughput screens holds tremendous potential for identifying new therapeutics for treating muscle disease. Already this strategy has lead to the development of promising therapeutic candidates now in clinical trial for DMD.
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