Targeting ER stress to treat osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a rare heritable disease characterized by bone fragility and deformity. OI is caused mainly by synthesis of abnormal or reduced amount of type I collagen, the main bone protein. Both dominant and recessive forms of the diseases had been described in human as caused by mutations in different genes. On the other hand the common bone phenotype of both dominant and recessive OI forms underlined the presence of common molecular basis. Specifically the intracellular accumulation of aberrant collagen is a common OI feature and it seems to us a good target to develop a common treatment. Various molecules, already FDA approved, exit that act on ER stress either helping aberrant protein folding or increasing their intracellular degradation. In this project we’re going to test these molecules in animal models and cells obtained from patients, being the final goal of our research to develop a novel pharmacological treatment for human OI.