Journal
MOLECULAR THERAPY-NUCLEIC ACIDS
Volume 12, Issue -, Pages 283-293Publisher
CELL PRESS
DOI: 10.1016/j.omtn.2018.05.011
Keywords
-
Categories
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [1F31AR068877]
- National Institute of Neurological Disorders and Stroke [5R01NS079568]
Ask authors/readers for more resources
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by a mutation in the dystrophin gene. Numerous gene therapies have been developed to replace or repair the defective dystrophin gene; however, these treatments cannot restore the full-length protein or completely resolve dystrophic symptoms. Secondary pathological mechanisms, such as functional ischemia and fibrosis, are thought to exacerbate the primary defect and cause the profound muscle degeneration found in dystrophic muscle. Surrogate therapies utilizing alternative therapeutic genes, or booster genes, such as VEGFA and utrophin, seek to address these secondary mechanisms and have shown impressive benefit in mdx mice. A skeletal muscle-specific microRNA, miR-206, is particularly overexpressed in dystrophic muscle and inhibits the expression of known booster genes. Thus, we aimed to determine if miR-206 contributes to dystrophic pathology by repressing beneficial gene expression. Here, we show that AAV-mediated expression of a miR-206 decoy target effectively downregulated miR-206 expression and increased endogenous therapeutic gene expression in mature mdx muscle. Furthermore, treatment significantly improved motor function and dystrophic pathology in mdx mice. In summary, we have identified a contributing factor to the dystrophic phenotype and characterized a novel therapeutic avenue for DMD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available