Duchenne Muscular Dystrophy (DMD) is caused by mutations in the gene coding for dystrophin, which functions to maintain muscle fiber structure and function, preventing it from being damaged by muscle contraction. Presently, there is no definitive treatment for DMD patients. Current therapies focus on prolonging survival and improving quality of life. Definitive treatment will require that functional dystrophin protein is restored in all affected muscle groups. Possible approaches include cell therapy, gene therapy or a combination of the two. We hope that transplantation of a particular type of muscle repair cell will help us to develop new therapeutic approaches to this disease. Muscle stem cells, termed satellite cells, isolated from healthy donors or patients should be able to provide dystrophin and repair muscle damage in DMD patients. For efficient therapy of DMD, satellite cells which maintain the self-renewing ability are necessary. Therefore, in this proposal, (1) we will focus on the study of how cultured satellite cells maintain their self-renewal capacity. In addition, systemic injection of satellite cells is an essential protocol that will provide healthy ells into all affected muscle tissues in DMD patients. Thus, (2) we will attempt to improve systemic delivery methods for satellite cells using a novel homing receptor expression. Furthermore, we need to use cells that are not rejected by a patient's immune system. (3) We are able to generate an unlimited number of satellite cells from induced pluripotent stem cells (iPSCs) derived from the patient's myoblasts. In combination with gene transduction, this concerted approach will help us to make satellite cells that can be transplanted into patients for a definitie cure of DMD.

Public Health Relevance

Duchenne Muscular Dystrophy (DMD) is caused by mutations in a gene called dystrophin, which acts to maintain muscle fiber structure and function, preventing it from being damaged by muscle contraction. Presently, there is no definitive treatment for DMD patients and current therapies focus on prolonging survival and improving quality of life. In combination with gene transduction of a functional dystrophin protein this concerted approach will enable us to make satellite cells that can be transplanted into patients for a definitive cure of DMD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR062142-02
Application #
8507146
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Nuckolls, Glen H
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$312,733
Indirect Cost
$98,983
Name
University of Minnesota Twin Cities
Department
Neurology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Asakura, Atsushi (2014) Grand challenges in the field of stem cell research. Front Cell Dev Biol 2:
Motohashi, Norio; Asakura, Atsushi (2014) Muscle satellite cell heterogeneity and self-renewal. Front Cell Dev Biol 2:
Motohashi, Norio; Asakura, Yoko; Asakura, Atsushi (2014) Isolation, culture, and transplantation of muscle satellite cells. J Vis Exp :
Ennen, James P; Verma, Mayank; Asakura, Atsushi (2013) Vascular-targeted therapies for Duchenne muscular dystrophy. Skelet Muscle 3:9