Exploring mitochondrial dysfunction in calpain-3 related muscular dystrophy

Limb-girdle muscular dystrophies are progressive diseases affecting muscle with onset usually in teens. Limb girdle muscular dystrophy type 2A is considered one of the most frequent form of LGMD and it is caused by mutation in a gene -CAPN3- which codes for a protein, calpain-3, with proteolytic activity. The exact pathogenetic mechanism that lead a mutation in CAPN3 to cause muscle dystrophy is still unclear, thus no therapeutic options are available for LGMD2A patients. Our hypothesis is that CAPN3 deficiency can be associated with mitochondrial impairment and oxidative stress, as suggested in a knock-out mouse model. These findings need to be tested and quantified also in patients’ tissue. We propose to test muscle tissue and muscle derived cells of patients with LGMD2A with experimental procedures that measure mitochondrial activities for which our lab has a long expertise. We will also test the effect of cyclosporin A, a drug with positive effect on mitochondrial activies which has been already proved to be helpful in some muscular dystrophies linked to mitochondrial impairment. Hopefully the results of this study will add novel information on the pathogenetic mechanism of LGMD2A and open for therapeutic possibilities.