Severe murine limb‐girdle muscular dystrophy type 2C pathology is diminished by FTY720 treatment

Limb‐girdle muscular dystrophy type 2C (LGMD‐2C) is caused by mutations in γ‐sarcoglycan and is a devastating, progressive, and fully lethal human muscle‐wasting disease that has no effective treatment. This study examined the efficacy of the sphingosine‐1‐phosphate receptor modulator FTY720 in treating Sgcg −/− DBA2/J, a severe mouse model of LGMD‐2C. FTY720 treatment was expected to target LGMD‐2C disease progression at 2 key positions by reducing chronic inflammation and fibrosis. Methods The treatment protocol was initiated at age 3 weeks and was continued with alternate‐day injections for 3 weeks. Results The treatment produced significant functional benefit by plethysmography and significant reductions of membrane permeability and fibrosis. Furthermore, the protocol elevated protein levels of δ‐sarcoglycan, a dystrophin–glycoprotein family member. Conclusion This study showed that FTY720 is an effective muscular dystrophy treatment when therapy is initiated early in the disease progression. Muscle Nerve 56 : 486–494, 2017