Anti Inflammatory
Blocking inflammatory agents
The degradation and death of muscle cells causes inflammatory processes which clean up the cell debris. Steroids are able to suppress inflammation, and this is probably one of the reasons why the drug 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. They are being widely used in Duchenne boys to maintain muscle function for at least a few years. But their exact mechanism of action is still not well known.
Sylvia Lopez a graduate student in the Laboratory of Dr. Melissa Spencer at the University in Los Angeles reported on new experiments to counteract inflammation and immune response and thus to find new ways to eventually replace the steroids with drugs that target specific immune mediated damage. Studies have shown that increased levels of the CD4 and CD8 T cells of the immune system accelerate the progression of the disease and that their inhibition reduces the rather slight dystrophic symptoms of mdx mice and very significantly the much more severe symptoms of the really sick utr-/mdx mice which in addition to the missing dystrophin also do not have any utrophin. This also extends the life span of these utophin-minus mdx mice. In addition, the amount of cytokines, molecules that promote inflammation and the development of fibrosis, is increased in mdx and Duchenne muscles.
Therefore, inhibition or removal of CD4 and CD8 T cells and also the modulation of active cytokines would possibly slow down the degradation of dystrophic muscles. A number of approved or potential anti-inflammatory drugs already exist. If they could be shown to positively influence Duchenne dystrophy, the time for the additional approval for the treatment of DMD could be considerably shortened. Three of the drugs are now being tested in Dr. Spencer’s laboratory to see whether they would be beneficial for Duchenne patients. They are already being tested in clinical trials for other diseases: CTLA-4Ig against rheumatoid arthritis, Galectin-1 is being lobbied and pushed into clinical trials for arthritis and has already been shown to improve muscle regeneration, and Anti-asialo GM1 an antibody being used in Parkinson's disease - just to name some of the target diseases. Testing of four other drugs will follow: Raptiva®, approved for psoriasis; Tisabri®, approved for multiple sclerosis and Crohn's disease; Remicade® and Enbrel®, 13 both approved for rheumatoid arthritis and other diseases. Long-term treatment studies will be necessary to establish whether these drugs could become therapies for Duchenne dystrophy and thus be able to improve the quality of life for Duchenne patients.
From Günter Scheuerbrandt Report of the PPMD Conference 2006