ROLE OF INTERLEUKIN-6 IN DUCHENNE MUSCULAR DYSTROPHY

The defect in the gene coding for dystrophin causes muscle pathology in Duchenne muscular dystrophy (DMD). The technical difficulties in developing gene therapy approaches have forced a renewed interest in exploiting non-genetic interventions. A possible target of non-genetic interventions is represented by therapeutic approaches aimed at inhibiting the inflammatory response in muscles of patients with DMD. Inflammation and inflammatory cells present in muscles play an important role in generating atrophy and in inhibiting regeneration, therefore promoting progression of muscle damage. Glucocorticoids, the most powerful anti-inflammatory agents, are at present used in the treatment because of their demonstrated ability to slow DMD progression. However, glucocorticoid treatment is only partially effective and is hampered by severe side effects; therefore, more effective and specific treatments with fewer side effects are needed. The exact inflammatory mechanisms and the pivotal inflammatory molecules involved are not yet known. Our preliminary data, as well as published evidence, support the hypothesis that a molecule, named interleukin-6, with marked pro-inflammatory activities may be a pivotal mediator of muscle inflammation in DMD. Osteoporosis with the increased frequency of fractures, causing immobilization and subsequent worsening of muscle hypotrophy and weakness, is a frequent complication of DMD. The cause of osteoporosis in DMD is not known. IL-6 is also a potential candidate for causing bone loss in these patients. The aim of this project is to prove the hypothesis that IL-6 is a pivotal mediator of muscle damage and bone loss in DMD. The 5 units will study muscle and bone in new animal models of muscular dystrophy and DMD patients in order to prove the role of IL-6 in vivo and to study the effects of IL-6 in patients. Proving the role of IL-6 will open new therapeutic perspectives based on anti-IL-6 therapy with an already available IL-6 inhibitor.