The objective of this proposal is to advance work towards a pharmaceutical therapy for FSHD. FSHD is caused by inappropriate expression of a protein known as DUX4. Inhibiting the activity of this protein with a small molecule that can be delivered systemically, i.e. a pharmaceutical, is a promising approach to developing a therapy.
This research represents a collaboration between the Kyba laboratory at the University of Minnesota, which has developed tools for screening small molecule inhibitors of DUX4 and animal models in which to test such potential drugs, and Icagen, a biotech focusing on high-throughput screening and early drug discovery. The two groups will collaborate to discover new small molecules and to develop them into potential new drugs targeting DUX4 for the treatment of FSHD.
Update July 2017
The objective of this collaborative project between the Kyba Laboratory and the biotech company Icagen is to discover and develop new small molecule inhibitors of DUX4 as potential therapeutics for FSHD. In this stage of the grant, we have performed a preliminary screen on a set of compounds enriched for known biological activities. This demonstrated that the screening protocol is suitable to automated 384-well screening and identified compounds with relatively weak, possibly indirect, biological activity. To further enhance the screening capabilities, we have developed improved high throughput screening cell lines and are currently validating these.