JP45 a functional modifier in ryanodinopathies

Skeletal muscles made up to 50% of the body mass, and loss of skeletal muscle contration has been recognised as a debilitating condition which affects the quality of life of individuals suffering of neuromuscular disorders. Muscle contraction is initiated by an electrical stimuli released by motor nerve. Such a electrical signal triggers an increase of the calcium concentration within muscle cells by a mechanism known as excitation-contraction coupling (ECC). Disregulation of EC coupling might be caused by mutation in the gene encoding the ryanodine receptor and dihydropyridine receptor, and it represents the molecular basis of neuromuscular disorders (malignat hyperthermia) and congenital myopathies such as Central Core Disease (CCD), multiminicore disease (MmD), centro nuclear myopathy (CMD). Individual affected by congenital myopathies carrying mutations in the ryanodine receptor gene show delayed motor development and their quality of life can be seriously jeopardised by the weakness of the skeletal muscle. The goal of this research project is two fold: a) understand the pathogenetic mechanisms of neuromuscular disorders linked to mutations in the ryanodine receptor gene; b) identify factors which modify the clinical symptoms of ryanodinopathies. The results of this study will be important to develop new interventions to improve diagnosis and therapy of neuromuscular disorders linked to mutations in the ryanodine receptor gene.