Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers reveal potential treatment for sickle cell disease

02.11.2011
Laboratory study at University of Michigan Health System shows increasing TR2/TR4 expression can lead to higher fetal hemoglobin levels in sickle cell patients

A University of Michigan Health System laboratory study reveals a key trigger for producing normal red blood cells that could lead to a new treatment for those with sickle cell disease.

The study, conducted in mice, appears in this week's early edition of the Proceedings of the National Academy of Sciences, and holds promise for preventing the painful episodes and organ damage that are common complications of sickle cell disease.

According to the U-M study, increasing the expression of the proteins, TR2 and TR4, more than doubled the level of fetal hemoglobin produced in sickle cell mice and reduced organ damage.

It's the first time specific proteins have been targeted to prevent a disease, authors say.

"The vast majority of sickle cell disease patients are diagnosed early in childhood when adult hemoglobin normally replaces fetal hemoglobin, but the severity of the disease can differ markedly, correlating most strongly with the level of fetal hemoglobin present in red cells," says pediatrician and lead study author Andrew D. Campbell, M.D., director of the Pediatric Comprehensive Sickle Cell Program at the U-M Cancer Center.

Sickle cell is an inherited blood disorder impacting hundreds of thousands of patients worldwide that causes normal red blood cells to change shape to a crescent moon.

The result is life-long debilitating pain episodes, chronic organ damage and significantly shortened life span. But a small number of sickle cell patients are born with a high enough fetal hemoglobin level to moderate these complications.

The study team, that included pediatric hematologists, cell and developmental biologists and pathology experts at U-M and the University of Tsukuba, Japan, demonstrated a potential method for boosting the fetal hemoglobin levels by modulating TR2/TR4 expression.

"While the average fetal hemoglobin was 7.6 percent in the sickle cell mice, the TR2/TR4 treated sickle cell mice had an average fetal hemoglobin of 18.6 percent," says senior study author James Douglas Engel, Ph.D. , professor and chair of the U-M's Cell and Development Biology Department.

He adds that anemia and red blood cell turnover all improved within the TR2/TR4 mice. Additional studies, including clinical trials, would be requiredto determine if the technique could help humans.

"Currently hydroxyurea is the only FDA approved drug known to increase the levels of fetal hemoglobin within sickle cell disease patients and a substantial number of patients do respond to it," says Campbell, the pediatric hematology oncology specialist. "But the long term consequences for hydroxyurea are unknown, especially in children."

Authors: Andrew D. Campbell, Shuaiying Cui, Lihong Shi, Rebekah Urbonya, Andrea Mathias, Kori Bradley, Kwaku O. Bonsua, Rhonda R. Douglas, Brittne Halford, Lindsay Schmidt, David Harro, Donald Giacherio, Keiji Tanimoto, Osamu Tanabe, and James Douglas Engel.

Reference: "Forced TR2/TR4 Expression in Sickle Cell Disease Mice Confers Enhanced Fetal Hemoglobin Synthesis and Alleviated Disease Phenotypes," Proceedings of the National Academy of Sciences, Oct. 31, 2011.

Funding: Authors work was supported by the American Heart Association, Cooley's Anemia Foundation, Robert Wood Johnson Foundation and the National Institutes of Health's National Heart Lung and Blood Institute.

Resources
Department of Cell and Developmental Biology
http://www.med.umich.edu/cdb/
U-M Sickle Cell Program
http://www.med.umich.edu/sicklecell/
University of Michigan Comprehensive Cancer Center
http://www.cancer.med.umich.edu/

Shantell M. Kirkendoll | EurekAlert!
Further information:
http://www.umich.edu

More articles from Studies and Analyses:

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>