Ricerc@Sapienza

The goal of the project is to produce satisfactory protocols in the treatment of Duchenne muscular dystrophy (DMD) through a specific aim: define the long term effects of IL-6 blockade on both skeletal and cardiac muscle.
One of the candidates that contribute to sustain an hostile microenvironment in dystrophic muscle is Interleukin-6 (IL-6), a critical player in the switch from acute to chronic inflammatory response. Previous studies suggest that: i) increased levels of IL-6 exacerbate the pathological phenotype of mdx mice; ii) blockade of endogenous IL-6 receptor, with neutralizing antibody, confers on dystrophic muscles resistance to degeneration.
Our working hypothesis is that the hostile dystrophic niche might interfere with and limit the efficacy of dystrophin replacement interventions. Thus, any therapeutic strategy aims to restore dystrophic muscle is unlikely to promote satisfactory results unless the hostile niche is modified.
Based on previous and preliminary data and in order to safely propose a therapeutic intervention aimed at blocking IL-6 transignaling in humans, we will define the long term-mediated effect of IL6r-alpha ablation on dystrophic skeletal and cardiac muscles. The achievement of this project will establish the viability of IL-6 as a therapeutic target opening a new perspective in the treatment of DMD.