In vivo models of myopathies and neuromuscular diseases

Myofibillar Myopathy and Muscular Dystrophy are life-threatening genetic diseases caused by mutations in genes necessary for both muscle satellite cells differentiation, such as myotilin and myogenin, and genes encoding for structural and shock absorber proteins necessary to protect muscle fibers from contractile stress, such as dystrophin, sarcoglycans and collagen VI. These diseases show common features such as early onset, muscle weakness and progressive loss of muscle tissue mainly affecting lower joint at early stage of disease development; heart and diafragm are affected in later stage and this is the main cause of death. There is no effective or generally applicable therapy for these diseases as most of mechanisms involved at early stages of pathogenesis are still unknown. Actual therapies are based on corticosteroids which act on inflammation but are unable to block disease progression and showed a lot of side effects. MY group, in an organic collaboration with both internal and external research groups at University of Brescia, PAdova, Verona and I.O.R. in Bologna, aims to dissect molecular mechanisms involved in the pathogenesis of myofibrillar myopathy and muscular dystrophy to identify new molecular targets to develop more effective and generally applicable therapies able to slow down disease progression and ameliorate patients' lives. As first step in that direction, we discovered molecules able to rescue from mitochondrial dysfunction at first stages of disease pathogenesis by restoring the intracellular Calcium homeostasis which is strongly deregulated in myopathic patients.