title: Carbamylated erythropoietin does not alleviate signs of dystrophy in mdx mice.
abstract: Erythropoietin promotes myoblast proliferation and inhibits fibrosis and thus it could impede the pathogenesis of muscle degenerative diseases. However, its stimulation of erythropoiesis limits its use as a therapeutic agent. An erythropoietin analog, carbamylated erythropoietin (C-EPO), retains these protective actions, yet it does not interact with the erythropoietin receptor. To determine whether treatment with C-EPO alleviates the signs of muscular dystrophy in an animal model of Duchenne muscular dystrophy, we treated mdx mice with intraperitoneal injections of 50 μg/kg and 100 μg/kg C-EPO for 4 and 12 weeks, and we monitored weight, serum creatine kinase levels, and changes in muscle histology. Moderate histological improvement was observed at 4 weeks, which did not translate into a significantly decreased level of serum creatine kinase. At the doses tested, C-EPO is not an effective therapeutic for the treatment of a mouse model of Duchenne muscular dystrophy.
authors.affiliation: Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Wu
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gussoni
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003402:Creatine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D018696:Neuroprotective Agents; C488171:carbamylated erythropoietin; D004921:Erythropoietin; D003402:Creatine Kinase