making muscle wasting history

The degradation and death of muscle cells in muscular dystrophy causes inflammatory cells to enter the muscle tissue to clean up the cell debris. Steroids are able to suppress inflammation, and this is probably one of the reasons why prednisone, its active form prednisolone, and the related deflazacort can increase muscle mass and strength and reduce the immune response, however often with some uncomfortable side effects. Prof. Melissa Spencer of the University of California
in Los Angeles and her team are performing experiments to find ways to replace the steroids with other drugs to counteract inflammation and immune response without their severe side effects.

Studies have shown that some cells of the immune system accelerate the progression of the disease. They produce cytokines, molecules that promote inflammation and the development of fibrosis in mdx and Duchenne muscles. In healthy people, this is a normal process of wound healing which stabilizes weak tissue and promotes healing.

In Duchenne boys, this healing process does not stop and the muscle undergoes a state of continuous wound healing. Therefore, it is hypothesized that the inhibition of immune cells and active cytokines might slow down the degradation and fibrosis of dystrophic muscles. A number of FDA approved anti-inflammatory drugs already exist which could possibly also act against these immune cells in Duchenne ystrophy. By testing drugs that are already FDA approved, the time to bring these drugs to Duchenne clinical trials will be shortened compared to new compounds. Three of these drugs used against other diseases are being tested in Dr. Spencer’s Laboratory on mdx mice: Galectin-1, Remicade®, and Enbrel®, all against rheumatoid arthritis and Anti-asialo GM1, an Antibody used in Parkinson’s disease.

Osteopontin is a protein which has many functions in bone biology, immune regulation, cell survival, inflammation, and cancer metastasis. Its concentration is increased in the blood and also in the muscles of mdx mice. Dr. Spencer has been examining osteopontin as a potential therapeutic target for Duchenne dystrophy. Mdx mice without osteopontin have better muscle strength, lower CK values, and reduced fibrosis. Work is now ongoing to find a drug which would inhibit osteopontin in Duchenne boys and thus become a candidate for a Duchenne therapy.