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Potential treatment for sickle cell disease

Date:
November 10, 2011
Source:
University of Michigan Health System
Summary:
Few options are available to prevent the painful episodes and organ damage that are common with sickle cell disease. But a new lab study has revealed a key trigger for producing healthy red blood cells that could lead to new treatments for 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 sickle cell disease.

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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.

"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 Comprehensive Cancer Center.

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

The result is debilitating pain episodes, chronic organ damage and a significantly shortened life span.

Sickle cell disease occurs in 1 out of every 500 African American births and 1 out of every 36,000 Hispanic American births, according to the Sickle Cell Disease Association of America, Inc.

It's most common among those with an ancestry to Africa, South and Central America, the Caribbean islands, India, Saudi Arabia and Mediterranean countries such as Turkey, Greece and Italy.

But a small number of sickle cell patients are born with a high enough fetal hemoglobin level to moderate complications.

The study team, that included experts in hematology oncology, cell and developmental biology and pathology from the 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.

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

Anemia and red blood cell turnover all improved within the TR2/TR4 treated mice. Additional studies, including clinical trials, would be required to determine if the method 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."


Story Source:

The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. D. Campbell, S. Cui, L. Shi, R. Urbonya, A. Mathias, K. Bradley, K. O. Bonsu, R. R. Douglas, B. Halford, L. Schmidt, D. Harro, D. Giacherio, K. Tanimoto, O. Tanabe, J. D. Engel. 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, 2011; DOI: 10.1073/pnas.1104964108

Cite This Page:

University of Michigan Health System. "Potential treatment for sickle cell disease." ScienceDaily. ScienceDaily, 10 November 2011. <www.sciencedaily.com/releases/2011/11/111102082806.htm>.
University of Michigan Health System. (2011, November 10). Potential treatment for sickle cell disease. ScienceDaily. Retrieved March 6, 2015 from www.sciencedaily.com/releases/2011/11/111102082806.htm
University of Michigan Health System. "Potential treatment for sickle cell disease." ScienceDaily. www.sciencedaily.com/releases/2011/11/111102082806.htm (accessed March 6, 2015).

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