Anti-fibrotics

Fibrosis is the process by which damaged tissue, for example, muscle tissue is replaced by fat and connective tissue. Fibrosis is similar to scarring and impedes the ability of the tissue to properly function. Scientists have observed that as the extent of fibrosis in muscle tissue increases, the function of the muscle decreases. Therefore, researchers are investigating whether muscle function can be protected by using medication such as anti-fibrotics, to reduce fibrosis. In this way it is hoped that muscle function in young people with Duchenne can be maintained as much as possible.

HT-100 is currently in phase I/II clinical development, being sponsored by Akashi Therapeutics, and is an inhibitor of TGF-β. TGF-β has emerged as a therapeutic target because of its role in the fibrotic process. Other inhibitors of this molecule have shown anti-fibrotic activity in Duchenne mouse models but are not currently under clinical development.

Connective tissue growth factor (CTGF/CCN2) is a protein that contributes to fibrosis and prevents muscle regeneration. Inhibition of this molecule could prevent development of fibrosis. FibroGen’s drug, FG-3019 is an antibody in phase 2 development which acts to inhibit CTGF and has been shown to reduce fibrosis whilst improving muscle function in mdx mice.