Generating FSHD‐affected human muscle in mice for testing therapeutic strategies

Investigator: Maura H Parker PhD

Category: Research - Translational

Great advances have been made to understand the cause of FSHD, and the mechanism behind the disease. Currently, there is a consensus that improper expression of the DUX4 protein in FSHD-affected muscle is the cause of the disease. Friends of FSH Research has invested in large screening efforts to identify potential drugs that inhibit DUX4; however, to further understand FSHD and test the safety and efficacy of these potential therapies, we need to develop an appropriate pre-clinical animal model. Mice are the most widely used animal model, as they are easy to handle and breed. However, they do not have the DUX4 gene in their genome, suggesting that simply introducing DUX4 alone into mouse muscle may be insufficient to model the human disease. In this project, we have proposed to generate human FSHD-affected muscle within mice using a novel techniques we developed performing canine to mice transplantation. These mice will be critical for studying diseased muscle in the context of an individual, yet sparing patients the pain of multiple muscle biopsies. Most importantly, these mice will be essential for pre-clinical testing of therapies that are currently being identified.

Supporting publication Activation of Notch signaling during ex vivo expansion maintains donor muscle cell engraftment​​​​​​

Supporting publication Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation