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Muscle Nerve ; 42(2): 218-29, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20589893

RESUMO

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.


Assuntos
Laminina/genética , Músculo Esquelético/patologia , Distrofia Muscular Animal/patologia , Piperidinas/farmacologia , Quinazolinonas/farmacologia , Animais , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Colágeno/biossíntese , Fibrose/tratamento farmacológico , Fibrose/patologia , Camundongos , Camundongos Knockout , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Distrofia Muscular Animal/terapia , Piperidinas/uso terapêutico , Quinazolinonas/uso terapêutico , Teste de Desempenho do Rota-Rod
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