Myotonic dystrophy (DM1), the most common form of muscular dystrophy in adults and children, is a multi- systemic, autosomal dominant genetic disorder caused by a mutation that leads to the production of a mutant RNA that is toxic to cells. Currently there are no therapies for DM1. Muscle weakness and wasting are major debilitating factors in DM1 and yet very little is known about the molecular mediators or muscle pathology in DM1. We have developed a mouse model of RNA toxicity in which we have demonstrated reversal of muscle pathology by silencing the toxic RNA. We have used this model to identify new molecules, mechanisms and pathways involved in RNA toxicity in DM1. This particular grant is designed to use genetic analysis and therapeutic trials in our mouse model to address the role of one of the novel molecules that we have identified in order to assess its potential as a viable therapeutic target. This novel finding opens new opportunities for: 1) understanding muscle degeneration, and perhaps cardiac pathology in DM1 and 2) developing new therapies to treat muscular dystrophy in DM1.

Public Health Relevance

Myotonic dystrophy (DM1) is the most common form of muscular dystrophy in adults and children. Currently there are no therapies. Muscle weakness and wasting are major debilitating factors. We have a novel finding that opens new opportunities for: 1) understanding muscle degeneration, and cardiac problems in DM1 and 2) developing new therapies to treat muscular dystrophy in DM1.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AR062189-04
Application #
8704879
Study Section
Skeletal Muscle Biology and Exercise Physiology Study Section (SMEP)
Program Officer
Boyce, Amanda T
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Virginia
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Charlottesville
State
VA
Country
United States
Zip Code
22904