The Monash team examined whether factors which promote the repair and regeneration of skeletal muscle can be utilized as possible therapeutic targets to reduce the debilitating muscle wasting that occurs in FSHD patients. They examined this hypothesis using a mouse model which was engineered using one of the FSHD disease candidate genes called FRG1. The FRG1 mouse exhibits muscle wasting and a disease prognosis similar to that observed in human FSHD patients. In a study published previously, Professor Mitchell and her team have identified a protein called FHL1 which they have shown is important for regulating muscle mass. Mice engineered to express elevated levels of FHL1 demonstrated increased muscle growth and strength, reduced muscle fatigue and are protected from age-related muscle weakness. Importantly these mice also exhibited increased numbers of muscle-stem cells (satellite cells) which facilitate the repair of damaged muscle. To determine if FHL1 was sufficient to reduce muscle wasting they have modified the FRG1 mouse model of FSHD to express increased levels of FHL1 and examined any potential therapeutic benefit to skeletal muscles.
The Monash team have further shown that muscle cells grown in the laboratory and engineered to contain increased levels of FRG1 show defects in the way they behave compared to normal muscle cells. They examined if these defects are also present in muscle cells isolated from the FRG1 mice, and if these defects contribute to muscle disease and finally if defects in these muscle cells can be rescued by FHL1