Update: Determining in vitro and in vivo efficacy of novel DUX4 inhibitors

Update by Dr. Ozes
See also Determining in vitro and in vivo efficacy of novel DUX4 inhibitors

Facioscapulohumeral dystrophy (FSHD) is a progressive disease commonly associated with loss of muscle in the face, scapula and humerus. FSHD affects 500,000 people worldwide and is incurable. Sadly, additional symptoms have also been associated with progressive disease that include vision changes, loss of hearing and abnormal heart rhythms.

Expression of Double Homeobox 4 (DUX4) protein in FSHD patients causes muscle cells to die overtime. Studies in human cells and in mice show that blocking DUX4 can stop further muscle death and could be a way to treat FSHD. However, there are currently no known drugs that bind and inhibit DUX4 directly.

At Altay, we developed an approach that can find drugs that block the activity of DNA binding proteins like DUX4. With the funding provided by Friends of FSH Research, we have identified the first-in-class small molecule inhibitor for DUX4. With the second grant, we have continued to develop our molecules and have significantly enhanced their physiochemical properties. Furthermore, we showed that our inhibitors bound to DUX4 in cell-based assays without altering normal muscle cell differentiation.

The combined data from these studies have now enabled us to choose the molecule with the best properties and begin testing their efficacy in mice in the next few months.