UCLA researchers have developed a new therapy that mimics the effects of hepcidin in mice. Iron in the body is regulated by a hormone called hepcidin, and a deficiency in this hormone can cause the iron overload seen in genetic disorders like hereditary hemochromatosis and Cooley's anemia. Published online Nov. 1 in the peer-reviewed Journal of Clinical Investigation, their findings could lead to new drugs to help prevent the condition.
Hepcidin works by fitting into a receptor protein known as ferroportin, which causes a change in iron flow in the body. The UCLA team systematically worked with the hormone-receptor interface to learn how the two pieces fit together and which part of hepcidin is the most important for binding to ferroportin.
"Like with jigsaw puzzle pieces, we tried to find the best fit," said Dr. Elizabeta Nemeth, the study's senior author and an associate professor of medicine at the David Geffen School of Medicine at UCLA.
Nemeth, co-director of the UCLA Center for Iron Disorders, noted that this is the first attempt to develop medications that mimic hepcidin. Because hepcidin contains 25 amino acids and numerous disulfide bonds, it would be expensive and difficult to reproduce the hormone as a medication.
The UCLA team zeroed in on the areas of hepcidin and ferroportin that provided the best fit to generate iron-regulating activity. Surprisingly, they found that the first third of the
Hepcidin molecule had an effect similar to that of the whole molecule. They then re-engineered this portion of the molecule to make it even more effective and named the resulting new molecules "minihepcidins."