Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder and the most frequent among muscular diseases. It is due to the deficiency of a protein called dystrophin and is characterized by progressive weakness and degeneration of the skeletal muscles. Since no cure for DMD has yet been found, there is an urgent need to identify new therapies. With this aim, we believe that drug repurposing is a powerful alternative approach to bring potential new therapies to the bedside.
Our drug discovery approach is based on unbiased phenotype-based screening of already approved molecules using simple DMD genetic avatars: worms and fish. Using those, we screened more than 4,500 molecules against the motility defect of dmd-mutant worms and identified 20 that could significantly ameliorate their symptoms. We are now currently validating their effect on dmd-mutant zebrafish that depict decreased swimming ability and muscle integrity defects. Interestingly, we identified one lead compound that is able to fully restore the swimming behaviour of dmd-mutant zebrafish after chronic exposure. We are now confirming the efficacy of our lead compound to restore muscle defects and prolong survival of dmd-mutant zebrafish. The next step will be to validate its efficacy in a mouse model of DMD and eventually to translate up to the clinic.