HEMOCHROMATOSIS: FROM GENES TO CLINICS

Hemochromatosis is a genetically and clinically heterogeneous disease characterized by excessive iron absorption leading to iron overload. The aim of this project is to transfer into clinics recent advances of basic research indicating that a common feature of these disorders is the deficiency of the hormone peptide hepcidin. First we will develop a stimulatory test based on urinary measurement of hepcidin after a single dose of oral iron, harmless for the patient, but able to induce hepcidin production in normal subjects. Through a collaborative prospective study of 100 patients, both at diagnosis and after iron depletion by phlebotomy, we will explore the diagnostic/prognostic value of this test. From the phlebotomy units collected from these patients monocytes/macrophages will be obtained and utilized to study defective iron release. Iron gene and protein expression will be analyzed to gain insights into the molecular mechanisms of the disease and to explore whether, as recently shown in vitro, hepcidin directly affects iron export also in vivo by modulating the function of its receptor ferroportin. The results of these studies are expected to be relevant for the differential diagnosis and treatment of iron disorders and to identify new molecular targets of potential therapeutic impact