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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AR052646-13
Application #
9330677
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Cheever, Thomas
Project Start
2005-09-25
Project End
2020-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
13
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Florida
Department
Pharmacology
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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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
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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
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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