Research Institution: University of Minnesota, Minneapolis USA

Principle Investigator: Dr Michael Kyba

Type: Study

Project title: “The development of an anti­DUX4 therapeutic based on chemical inhibitors of DUX4”

Status: Completed


This grant was supplementary support linked to a National Institutes of Health (USA) NIH R21 (2-year) grant directed towards identifying chemical drugs that inhibit the genetic material (gene) called DUX4, which has been associated with causing FSHD. Dr Kyba’s group had previously screened 200,000 compounds and identified approximately 600 drugs inhibiting the cell death induced by the DUX4. Their current work is directed towards identifying the most promising drugs for treatment of FSHD, within this set of 600. Using the support from FSHD Global, they performed additional screens on panels of chemicals known to be active in treating other diseases and in doing so identified several additional drugs inhibiting the DUX4-toxicity. The chemicals Dr Kyba’s group has identified may help us to understand the chemical pathways that can indirectly inhibit the muscle toxicity associated with the DUX4 gene. In the past 6 months, they have obtained approximately 50 chemicals from the set of 600 identified, for further testing. The majority of these 600 chemicals fall into 20 different groups, known as “chemical series”, that have similar chemical structures. Dr Kyba’s group repeated the initial screening of these chemicals, for protection of cells from DUX4-induced death, using the independently obtained compounds and they have now begun additional tests to understand how these compounds work and what chemical pathways they impact. Their objective now is to narrow down this set of 20 chemical series to identify the 2-4 that are most suitable for drug development for effective treatment of FSHD.