This MDCRC is organized around the central theme of improving muscle regeneration in a number of types of muscular dystrophy by inhibiting fibrosis and limiting fatty replacement of muscle, thus improving skeletal muscle repair and preserving cardiac function. Interacting and collaborative studies are proposed to address by what mechanisms muscle fibrosis and fat deposition occur. Project 1 is focused on understanding the pathways and cell types that contribute to inflammation, fibrosis, and fatty deposition. Project 1 will evaluate a number of potential therapeutics, utilizing an exciting new mouse model of DMD, the mdx mouse on the DBA background, which may greatly accelerate successful drug translation. Project 2 is focused on identifying and characterizing modifiers of cardiac disease, which in many cases will be modifiers of skeletal muscle disease as well. Project 3 will gain insights into how genetic variations in LTBP4 and Osteopontin impact imaging biomarkers of disease in the heart, respiratory muscles, and leg muscles of DMD patients. In doing so, Project 3 will develop MRI/MRS protocols for monitoring disease progression in the respiratory muscles.
In many types of muscular dystrophy, muscle fails to repair itself, and is gradually lost and replaced with fat and connective tissue. This MDCRC is a coordinated effort to understand the nature of the disease processes that prevent muscle repair and maintenance, and to evaluate therapeutics that will alter the course of disease. Ultimately, this Center will provide the insights, tools, and therapeutic validation needed to support clinical trials that will lead to the slowing of the progression of Duchenne (DMD) and other forms of muscular dystrophy.
|Smith, Lucas R; Barton, Elisabeth R (2018) Regulation of fibrosis in muscular dystrophy. Matrix Biol 68-69:602-615|
|Hicks, Michael R; Hiserodt, Julia; Paras, Katrina et al. (2018) ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs. Nat Cell Biol 20:46-57|
|Barnard, Alison M; Willcocks, Rebecca J; Finanger, Erika L et al. (2018) Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy. PLoS One 13:e0194283|
|Fallon, Justin R; McNally, Elizabeth M (2018) Non-Glycanated Biglycan and LTBP4: Leveraging the extracellular matrix for Duchenne Muscular Dystrophy therapeutics. Matrix Biol 68-69:616-627|
|Batra, Abhinandan; Harrington, Ann; Lott, Donovan J et al. (2018) Two-Year Longitudinal Changes in Lower Limb Strength and Its Relation to Loss in Function in a Large Cohort of Patients With Duchenne Muscular Dystrophy. Am J Phys Med Rehabil 97:734-740|
|Daniel, Bence; Nagy, Gergely; Czimmerer, Zsolt et al. (2018) The Nuclear Receptor PPAR? Controls Progressive Macrophage Polarization as a Ligand-Insensitive Epigenomic Ratchet of Transcriptional Memory. Immunity 49:615-626.e6|
|Willcocks, Rebecca J; Triplett, William T; Lott, Donovan J et al. (2018) Leg muscle MRI in identical twin boys with duchenne muscular dystrophy. Muscle Nerve :|
|Aartsma-Rus, Annemieke; Ferlini, Alessandra; McNally, Elizabeth M et al. (2018) 226th ENMC International Workshop:: Towards validated and qualified biomarkers for therapy development for Duchenne muscular dystrophy 20-22 January 2017, Heemskerk, The Netherlands. Neuromuscul Disord 28:77-86|
|Barthélémy, Florian; Defour, Aurélia; Lévy, Nicolas et al. (2018) Muscle Cells Fix Breaches by Orchestrating a Membrane Repair Ballet. J Neuromuscul Dis 5:21-28|
|McNally, Elizabeth M; Wyatt, Eugene J (2017) Mutation-Based Therapy for Duchenne Muscular Dystrophy: Antisense Treatment Arrives in the Clinic. Circulation 136:979-981|
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