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
Shantell M. Kirkendoll | EurekAlert!
Virtual "moonwalk" for science reveals distortions in spatial memory
18.11.2019 | Max-Planck-Institut für Kognitions- und Neurowissenschaften
Autonomous Agriculture in 2045?
15.11.2019 | Fraunhofer-Institut für Experimentelles Software Engineering IESE
Conventional light microscopes cannot distinguish structures when they are separated by a distance smaller than, roughly, the wavelength of light. Superresolution microscopy, developed since the 1980s, lifts this limitation, using fluorescent moieties. Scientists at the Max Planck Institute for Polymer Research have now discovered that graphene nano-molecules can be used to improve this microscopy technique. These graphene nano-molecules offer a number of substantial advantages over the materials previously used, making superresolution microscopy even more versatile.
Microscopy is an important investigation method, in physics, biology, medicine, and many other sciences. However, it has one disadvantage: its resolution is...
Nanooptical traps are a promising building block for quantum technologies. Austrian and German scientists have now removed an important obstacle to their practical use. They were able to show that a special form of mechanical vibration heats trapped particles in a very short time and knocks them out of the trap.
By controlling individual atoms, quantum properties can be investigated and made usable for technological applications. For about ten years, physicists have...
An international team of scientists, including three researchers from New Jersey Institute of Technology (NJIT), has shed new light on one of the central mysteries of solar physics: how energy from the Sun is transferred to the star's upper atmosphere, heating it to 1 million degrees Fahrenheit and higher in some regions, temperatures that are vastly hotter than the Sun's surface.
With new images from NJIT's Big Bear Solar Observatory (BBSO), the researchers have revealed in groundbreaking, granular detail what appears to be a likely...
The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Dresden has succeeded in using Selective Electron Beam Melting (SEBM) to...
Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.
New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...
15.11.2019 | Event News
15.11.2019 | Event News
05.11.2019 | Event News
20.11.2019 | Life Sciences
20.11.2019 | Physics and Astronomy
20.11.2019 | Health and Medicine