Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Design Experimental Treatment for Iron-Overload Diseases

03.11.2011
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:
http://www.mednet.ucla.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

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: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>