Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Scientists Design Experimental Treatment for Iron-Overload Diseases

Iron overload is a common condition affecting millions of people worldwide. Excess iron in the body is toxic, and deposits can cause damage to the liver, heart and other organs. Current treatments, researchers say, are not ideal and have significant side effects.

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
Further information:

More articles from Health and Medicine:

nachricht Scientists develop tiny tooth-mounted sensors that can track what you eat
22.03.2018 | Tufts University

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Modular safety concept increases flexibility in plant conversion

22.03.2018 | Trade Fair News

New interactive map shows climate change everywhere in world

22.03.2018 | Earth Sciences

New technologies and computing power to help strengthen population data

22.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>