title: Severe murine limb-girdle muscular dystrophy type 2C pathology is diminished by FTY720 treatment.
abstract: 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.
  
  
  
  The treatment protocol was initiated at age 3 weeks and was continued with alternate-day injections for 3 weeks.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, 835 South Wolcott Avenue, COMRB 2035, MC 901, Chicago, Illinois, 60612, USA.|The Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Ahlke
authors.initials: A
authors.lastname: Heydemann
mesh_terms: D000818:Animals; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011897:Random Allocation; D058088:Sarcoglycanopathies / Q000188:drug therapy* / Q000473:pathology*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: FTY720; dystrophin-glycoprotein complex; fibrosis; mouse model; muscular dystrophy; sphingosine-1-phosphate