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.
Journal of Clinical Investigation
Structure of the human hormone hepcidin (top panel) and the portion used for the minihepcidin design (bottom panel).
In the hopes of finding a treatment for iron overload, UCLA researchers have developed a new type of therapy based on small molecules that mimic the effects of hepcidin in mice. 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."
"We found that just a few amino acids were enough to provide an effective scaffold for the minihepcidin design," said Piotr Ruchala, a visiting assistant professor of medicine at the Geffen School of Medicine.
The team confirmed that the minihepcidins were effective in healthy mice and demonstrated that they could prevent iron overload in mouse models of hereditary hemochromatosis.
"Using this structure and function analysis, we were able to develop minihepcidins that were even more effective than the naturally occurring hormone," said study author Dr. Tomas Ganz, a professor of medicine and pathology and co-director of the Center for Iron Disorders at the Geffen School of Medicine.
Ganz added that the UCLA findings built on previous research by the team and collaborators around the world that originally helped identify the role of hepcidin and ferroportin in iron regulation.
The next step is to identify the optimal form of minihepcidin for human trials. According to UCLA researchers, if the molecules' safety and efficacy is confirmed, minihepcidins could be used alone or together with current treatments for iron-overload diseases.
The study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases, which is part of the National Institutes of Health, and the Will Rogers Fund.
UCLA is currently negotiating a license to this technology with a biotechnology company that will take the minihepcidins through pre-clinical development and into clinical trials.
Other study authors included Gloria C. Preza of the UCLA Department of Pathology; Rogelio Pinon and Bo Qiao of the UCLA Department of Medicine; Emilio Ramos of the UCLA Department of Chemistry and Biochemistry; Michael Peralta of the Columbia University Department of Chemistry; Shantanu Sharma of the California Institute of Technology's Materials and Process Simulation Center; and Alan Waring of the UC Irvine School of Medicine's Department of Physiology and Biophysics.
For more news, visit the UCLA Newsroom and follow us on Twitter.
Rachel Champeau | Newswise Science News
Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign
Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences