Clenbuterol to Target DUX4 in FSHD

Clenbuterol is an EMA approved drug for COPD that three independent patient derived screens identified as suppressing DUX4 expression in cultured FSHD muscle. Prior clinical studies with related beta2-agonists showed some activity in FSHD but did not meet their primary endpoint, although the prior studies would likely have been designed differently with current knowledge. Target FSHD is a 6-month open-label multiple ascending dose study of clenbuterol for safety and tolerability to determine the best dose for a future trial of efficacy. In addition, this study will collect secondary outcome data on muscle function, MRI changes (lean muscle volume, fat infiltration, STIR-rating) and molecular markers of disease activity (histopathology and pre-determined baskets of DUX4-target, inflammation, and ECM genes) at the beginning and end of the study to assess and power their utility as measures of drug activity in a future interventional study of efficacy.