Researchers Find New Genetic Target for Sickle Cell Disease Therapy
Treatments developed over the past three decades have led to the doubling of the life expectancy of sickle cell disease patients between 1972 and 2002. These treatments include medications, blood and bone marrow transfusions, and other procedures to relieve or prevent complications. Until now, however, scientists could not directly target processes known to affect the severity of sickle cell disease.
Balintfy: An article published online in Science on December 4th describes a discovery that could lead to new treatment targets for some inherited blood diseases:
Shurin: The findings in this article are applicable to both people with sickle cell sickle cell disease and thalassemia, or are at least potentially applicable to them.
Balintfy: Dr. Susan Shurin is the National Heart, Lung and Blood Institute deputy director. She says these are genetic disorders that affect approximately seventy-thousand people in the United States, primarily African-Americans.
Shurin: These are diseases that affect many millions of people world wide. These are very big public health problems, particularly in sub-Saharan Africa and the Middle East, in the Mediterranean and also in Southeast Asia.
Balintfy: These disorders also have a very high health burden, making them difficult to deal with in terms of both symptoms and treatment, which can include medications and blood transfusion.
Shurin: For people with sickle-cell disease they tend to have a lot of pain. And for both thalassemia and sickle-cell disease particularly if people are not transfused early in life these may be fatal diseases.
Balintfy: A form of hemoglobin, which is the protein in the blood that makes red blood cells red, and carries oxygen from the lungs to tissues in the body, is involved in both these diseases. Dr. Shurin explains that in sickle cell disease, hemoglobin is abnormal and sticks together. The red blood cells become stiff and sickle-shaped, causing them to block blood vessels and rob tissues of necessary blood and oxygen. In thalassemia, the body has trouble producing adult forms of hemoglobin.
Shurin: So what this study shows, is it lays the groundwork for the development for some targeted therapies which are of potential major benefit for people with both thalassemia and sickle-cell disease.
Balintfy: Researchers are reporting that by suppressing or "turning off" a gene called BCL11A, production of a form of hemoglobin improves dramatically.
Shurin: So there are going to be two really key issues here. The first is to try to find some good ways of targeting this so we can decrease the production of BCL11A, or inactivate it once it's present in a cell, that would be number one. And number two is to try to do this so we do it as specifically as possible for red blood cells so we get as few side effects in other tissues as possible.
Balintfy: Dr. Shurin adds that both the results and methodology in the study may help move treatment options forward to tests in mice, possibly within the next couple years. For more information on this study and these blood disorders, visit www.nhlbi.nih.gov. This is Joe Balintfy, National Institutes of Health, Bethesda, Maryland.