Combating fibrosis in mdx mice with a novel antifibrosis drug - Halofuginone

Abstract

The effects of the antifibrotic drug Halofuginone hydrobromide (Halo) on muscle function, regeneration and cardiorespiratory function were studied using mdx mice. It was hypothesized that Halo treatment would resolve pre-established fibrosis and prevent collagen deposits, improving muscle and cardio-respiratory function. Mice 8-9 mos were treated with saline or Halo for 5 (n = 4/group), 10 (n = 5/group) and 12 weeks (n = 4-5/group). Muscle strength and endurance, respiration and muscle susceptibility to damage were assessed. Tissues were collected from all mice. Additional mice were treated for 10 wks (3-4 wks n = 9-10/group; 8-9 mos n = 8-9/group) for echocardiography. Halo reduced fibrosis. As a consequence, there was muscle repair and damage was reduced. There were functional improvements and disease progression was slowed. There was resolution of pre-existing fibrosis and reduction of new collagen synthesis. This treatment could improve quality of life and lengthen the lifespan of DMD patients.