TARGETED PATHWAY INHIBITION TO IMPROVE MUSCLE STRUCTURE, FUNCTION AND ACTIVITY IN MUSCULAR DYSTROPHY

摘要

A pathway that can be targeted for the treatment of or alleviation of symptoms of Duchenne Muscular Dystrophy (DMD) has been identified. Compounds have been identified and tested in a zebrafish model of DMD and found to be efficacious based on an increase in the survival rate of dystrophin deficient fish. Several of the compounds are in the PDE inhibitor pathway. Additional components of the pathway not inhibited by PDE inhibitors but active in the zebrafish assay are screened for their inhibition of NFK-β and increase heme oxygenase- 1. In some embodiments, these compounds influence blood flow to skeletal muscle. In some embodiments, the combined pathway leading to inhibition of NFK-β and increase in heme oxgenase- 1 is important in identification of compounds effective in the treatment or alleviation of symptoms of DMD.