Discovery could improve anemia treatment in patients

ext step is to determine whether drugs that inhibit HFE or hepcidin will be useful," says Senior Investigator Dr. Nancy Andrews, a Howard Hughes Medical Institute investigator at Children's Hospital Boston and the Leland Fikes Professor of Pediatrics at Harvard Medical School.

Roy notes that it may not be desirable to inactivate hepcidin completely. The hormone's antimicrobial properties would be lost and allowing too much iron to circulate also can promote infection. "It's going to be a balance," Roy says. "If we manipulate hepcidin activity, we have to be very careful not to encourage infection while we're trying to resolve the anemia. The ideal would be to control infection while allowing enough iron for red blood cell production."

HFE has long been known to control iron absorption. Andrews' lab has previously shown that a lack or a defect in HFE causes an opposite condition -- hereditary hemochromatosis (iron overload). People with this condition absorb too much iron, and as iron levels build up, they can develop liver cancer, heart disease, and other fatal conditions. "Living organisms have evolved intricate mechanisms to regulate iron uptake and distribution so they can exploit iron's useful properties while avoiding toxicity," notes Andrews.

Andrews and Roy are intrigued by the interaction of HFE and hepcidin, because it suggests that HFE has an immunologic function as well as an iron-regulating function. "We don't yet understand the immunity connection," says Andrews, who also holds a doctorate in biology. "Many molecules important in iron metabolism are also involved in immune defense, or are related to molecules involved in immune defense. But we don't yet know why." EMBL Scientists Martina Muckenthaler and Matthias Hentze collaborated closely with the Children's/Harvard team to identify this link.

"Our results clearly link HFE to the development of this type of anemia. More importantly, it seems that you can affect HFE f

Contact: Mary-Ellen Shay
Children's Hospital Boston

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