Ahlke Heydemann1,2. 1. Department of Physiology and Biophysics, University of Illinois at Chicago, 835 South Wolcott Avenue, COMRB 2035, MC 901, Chicago, Illinois, 60612, USA. 2. The Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois, USA.
Abstract
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.
INTRODUCTION:Limb-girdle muscular dystrophy type 2C (LGMD-2C) is caused by mutations in γ-sarcoglycan and is a devastating, progressive, and fully lethal humanmuscle-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.
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