making muscle wasting history

The transforming growth factor beta (TGFβ) is a protein which inhibits the satellite cells (muscle stem cells) from regenerating muscle tissue. Mdx mice and also Duchenne boys have increased amounts of TGFβ, and this leads to fibrosis (scar tissue), which is caused by the excessive production of connective tissue and its deposition between the muscle fibers in turn replacing degraded and lost fibers. Under normal circumstances, connective tissue holds the muscle fibers together, but increased levels lead to muscle stiffness and contractures. Connective tissue consists mainly of the protein collagen, a rather inelastic molecule that is generated by fibroblasts. Thus inhibiting the activity of TGFβ with drugs may be a possible way to reduce fibrosis.

Prof. Andrew Hoey of the University of Southern Queensland in Toowoomba, Australia, and his co-workers tested pirfenidone which is an approved medication for treatment of fibrosis in the lungs. Eight-month old mdx mice were administered this drug and after seven months of treatment showed reduced levels of TGFβ and restored heart function almost to normal, but fibrosis was not reduced in these old mdx mice. The possibility of the drug being more effective in younger mice will be examined in future experiments.