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

INTRODUCTION: 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.