Title:
Compounds for treating Facioscapulohumeral Muscular Dystrophy and method for discovering
Category:
Therapeutic and Research Tool
NCS:
Inventors: Francis M. Sverdrup, Stephen J. Tapscott
Summary:
Facioscapulohumeral Muscular Dystrophy (FSHD) is characterized by epigenetic changes resulting in the aberrant expression of the DUX4 gene in muscle. Suppression of DUX4 expression is considered a therapeutic target for FSHD. But the mechanisms responsible for DUX expression are poorly understood and few targets are known amenable for small molecule drugs. A method is disclosed for using a unique cell based assay that detects DUX4 expression and activity in differentiating FSHD muscle cells to screen for compounds that target epigenetic modifying proteins. This “chemical genetics” approach identified BET bromodomain proteins as key targets involved in DUX4 expression. Inhibitors of BET bromodomain proteins block induction of DUX4 expression/activity in our screening assay. They are further shown to block the induction of DUX4 mRNA and the mRNA of its downstream targets ZSCAN4 and TRIM43.
Patent:
U.S. patent application – 61/880,565
Manager:
Stephanie Kimzey, MBA