Inflammation in Duchenne Muscular Dystrophy (DMD) increases the production of connective tissue fibrosis. No current treatment has been effective in eliminating or reducing the build up of collagen fibers. A newly discovered anti-fibrotic drug, halofuginone, promotes recovery and prevents fibrosis. The current study examines the effectiveness of halofuginone in treating and preventing fibrosis in mdx mice. It was hypothesized that halofuginone treatment would resolve pre-established fibrosis and prevent collagen deposits, improving muscle and cardio-respiratory function. Mice (8-9 months old) were treated with saline or halofuginone for 5, 10 and 12 weeks. Muscle strength and endurance, respiration and muscle susceptibility to damage were assessed. Northern blots, Sirius red stains, immunofluorescence, and in-situ hybridization were used to evaluate histochemical and molecular pathologies of the diaphragm, heart, quadriceps and tibialis anterior. Echocardiography was performed at 0, 5, and 10 weeks. Halofuginone prevented and reduced fibrosis in mdx mice, leading to functional recovery and delayed disease progression. If halofuginone proves successful in mice, this treatment has the potential to improve quality of life and lengthen the lifespan of DMD patients.


Références : Am J Physiol Heart Circ Physiol. 2008 Feb 8; [Epub ahead of print]