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Severe murine limb‐girdle muscular dystrophy type 2C pathology is diminished by FTY720 treatment
Author(s) -
Heydemann Ahlke
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25503
Subject(s) - limb girdle muscular dystrophy , muscular dystrophy , medicine , fibrosis , wasting , dystrophin , rheumatology , pathology , endocrinology , biology , mutation , biochemistry , gene
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