Progress Update: Testing the effects of antifibrotic drugs on an FSHD mouse model and FSHD fibroadipoprogenitors: the first step toward antifibrotic therapy for FSHD

Posted by Friends of FSH Research on Dec 8, 2021

Report by Darko Bosnakovski
See grant Testing the effects of antifibrotic drugs on an FSHD mouse model and FSHD fibroadipoprogenitors: the first step toward antifibrotic therapy for FSHD

Emerging evidence suggests a crucial role of fibroadipogenic progenitors (FAPs) in muscle homeostasis. Fibrosis is one of the most predominant pathological features of the affected muscles in FSHD patients. The substitution of the muscle tissue with fibrous and fatty tissue progresses over time,directly impacts muscle physiology and skeletal mobility. Thus, controlling or reverting fibrosis may decrease progressive muscle damage and promote muscle regeneration. We know very little about FAPs and muscle fibrosis in FSHD patients. Therefore, this project aims to better understand the fibroadipogenic process in FSHD and test the effectiveness of various antifibrotic drugs to reduce muscle degeneration in an FSHD mouse model.

Despite setbacks due to the pandemic, we are satisfied to report that we accomplished most of the planned tasks in the first six months. Our main achievement is generating a collection of primary cell lines (FAPs and myoblasts) from muscle biopsies from FSHD patients and healthy donors. These cell lines are a necessary tool for studying the fibroadipogenic properties of FSHD FAPs and testing the effectiveness of the antifibrotic drugs in vitro. Furthermore, we initiated the in vivo experiments in which we explored the benefit of antifibrotic drugs in reducing muscle degeneration provoked by DUX4 in iDUX4;HSA FSHD mouse model.