Background: progressive atrophy and fat infiltration is observed in DMD muscles. In a phase II study Givinostat was shown to increase muscle area and reduce muscle necrosis, fibrosis, and fat replacement in muscle biopsies taken after 12 months of treatment.
Objective: to evaluate the effects of Givinostat on atrophy and fat infiltration (FI) measured by MRI.
Methods: 17 patients enrolled in the aforementioned phase II study underwent MRI at baseline and after 2 years of treatment with Givinostat. The effects of Givinostat on atrophy and FI were compared to a natural history cohort of 13 patients matched by age, steroid treatment and 6 Minute Walk Distance at baseline. Muscles were analyzed at baseline and and after 24 months singularly and by compartments. A total of 60 MRI studies were analyzed. Atrophy and FI were evaluated with a semiquantitative scale (0-1-2-3) and (1-2-3-4) by 2 independent readers blinded to treatment and sequence.
Results: At baseline the highest atrophy scores were in the Glutei, and in the Thighs (medial, anterior and posterior compartments). The FI scores followed the same pattern with the Glutei and the thigh being more affected than the leg. After two years atrophy increased in the Glutei and Thighs with little changes in the Legs. FI worsened in all compartments. When the changes in atrophy and FI were compared between Givinostat and control patients using Bayesian statistics, atrophy was increasing less in givinostat in the Glutei and Anterior Thigh compartment, while FI was increasing less with Givinostat in the Anterior Thigh and Posterior Leg compartments (Probability >80%).
Conclusions: Atrophy scores increase even if the impact is smaller than pseudohypertrophic evolution.
Fat infiltration increases in all compartments with age.
Our results suggest that Givinostat reduces atrophy and fat infiltration progression.