CELL/GENE TRANSFER IN IPEX

The syndrome known as Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) is a severe disease due to mutation of a gene called FOXP3, transmitted to male children from the healthy carrier mothers. The disease begins in early infancy with untreatable diarrhea, usually accompanied by insulin-dependent diabetes mellitus and eczema, with elevated serum IgE. Although rare, the disease is often fatal, and presently, there is no real therapy since the immunosuppressive drugs are only partially efficacious, and bone marrow transplantation has been performed in a limited number of cases. The FOXP3 gene if mutated in animal models, leads to an impaired development of regulatory T cells (Tr), a key T cell subset for keeping the immune system under control and preventing autoimmunity. However, in humans a correlation between the FOXP3 mutation and the mechanisms responsible for the autoimmune pathology has still to be defined. The present research is focused on cellular and molecular studies of cells isolated from IPEX patients, aimed at unravelling the immune mechanisms that are disrupted in mutated FOXP3 cells. In addition, using gene transfer techniques to replace the mutated gene, we will test the feasibility of correcting in vitro the molecular defect, thus setting the basis for a gene therapy approach. The outcome of these studies on IPEX as a disease model, will be instrumental for generating innovative strategies to treat also other more common diseases caused by altered immune responses.