title: Fibrosis inhibition and muscle histopathology improvement in laminin-alpha2-deficient mice.
abstract: In muscular dystrophies (MD) the loss of muscle and its ability to function are associated with fibrosis. We evaluated the efficacy of halofuginone in reducing fibrosis in the dy(2J)/dy(2J) mouse model of congenital MD. Mice were injected intraperitoneally with 5 microg of halofuginone 3 times a week for 5 or 15 weeks, starting at the age of 3 weeks. Halofuginone caused a reduction in collagen synthesis in hindlimb muscles. This was associated with reductions in the degenerated area, in cell proliferation, in the number of myofibers with central nuclei, with increased myofiber diameter, and with enhanced motor coordination and balance. Halofuginone caused a reduction in infiltrating fibroblasts that were located close to centrally nucleated myofibers. Our results suggest that halofuginone reduced the deleterious effects of fibrosis, thus improving muscle integrity. Halofuginone meets the criteria for a novel antifibrotic therapy for MD patients.
authors.affiliation: Neuropediatric Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Nevo
authors.forename: Orna
authors.initials: O
authors.lastname: Halevy
authors.forename: Olga
authors.initials: O
authors.lastname: Genin
authors.forename: Itai
authors.initials: I
authors.lastname: Moshe
authors.forename: Tidhar
authors.initials: T
authors.lastname: Turgeman
authors.forename: Michal
authors.initials: M
authors.lastname: Harel
authors.forename: Edva
authors.initials: E
authors.lastname: Biton
authors.forename: Shimon
authors.initials: S
authors.lastname: Reif
authors.forename: Mark
authors.initials: M
authors.lastname: Pines
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D007797:Laminin / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology* / Q000628:therapy; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D052999:Quinazolinones / Q000494:pharmacology* / Q000627:therapeutic use; D045442:Rotarod Performance Test
chemical_list: D007797:Laminin; D010880:Piperidines; D052999:Quinazolinones; C102645:laminin alpha 2; D003094:Collagen; C010176:halofuginone