C1q inhibition in muscular dystrophy

Although under normal conditions muscle stem cells present a very powerful regenerative response, the regenerative potential is progressively lost in patients affected by Duchenne Muscular Dystrophy and fibrotic tissue progressively replaces muscle fibers leading to an impairment of muscle function. Fibrosis itself both contributes to the symptomatology of Duchenne Muscular Dystrophy and is also a barrier to effective therapies (in particular for cell and gene therapy approaches). The cellular and molecular mechanism leading to fibrosis in Duchenne Muscular Dystrophy is still largely unknown. Recent observations from our laboratory are suggesting that aberrant complement accumulation in dystrophic muscles may play a detrimental role. The overall aim of this study is to explore these aspects further, and investigate the potential beneficial effects of complement therapeutics in dystrophic animal models. Molecular, histological and functional muscle amelioration will be evaluated in dystrophic mice upon inhibition of the C1q component of the C1 complex. Both genetic and pharmacological approaches will be employed to this goal. This study may represent an important step toward the development of effective therapeutic approaches and the repurposing in Duchenne muscular dystrophy of complement-targeting drugs currently used to treat other pathological conditions.