BACKGROUND: Sickle cell disease is a disorder of red blood cells, specifically the part of the red blood cell that carries oxygen. It is most common in African Americans. The disease causes red blood cells to change from the normal, round shape to a sickle shape. When this happens, they can't flow through the small blood vessels and get stuck, building up a "traffic jam." When this happens, areas of the body do not get enough blood or oxygen and the result is pain.
The physiological cause is similar to that of the pain from a heart attack. Patients often end up requiring hospitalization to help open the blood vessels and get more oxygen in the blood.
Sickle cell disease also has a number of secondary effects that can result in early death. The condition can damage the brain, kidneys, liver and other organs. The most common cause of death is kidney failure.
GOING TO THE CAUSE: Researchers have known for years that there are three different stages of hemoglobin differentiation -- embryonic, fetal and adult. It is the adult hemoglobin that can be the problem. On the other hand, researchers say people in the sickle cell population who have high levels of fetal hemoglobin tend to have less severe disease. Therefore, researchers from the University of Illinois at Chicago reasoned that if they could find a way to turn on the gene for fetal hemoglobin that turned off during development, they might be able to help this group.
Joe DeSimone, Ph.D., and researchers at UIC, are studying the cancer drug decitabine to treat people with sickle cell disease. Decitabine causes changes in the DNA that allows genes that have been turned off to be turned back on.
STUDY: As more research is done on the drug and how it can help patients with sickle cell, doctors are looking for different and better ways to deliver it. First, they delivered it via IV. Now they're doing it subcutaneously, and the goal is to find a way to give it orally. The subcutaneous delivery is done twice a week and so far appears to be well-tolerated.
The drug has been used on patients who have failed the gold standard treatment, hydroxyurea, and, according to DeSimone, all have responded. In these patients, fetal hemoglobin levels went from less than three percent to greater than 20 percent.
"When this happens, the secondary effects... those abnormalities decrease when we elevate fetal hemoglobin levels," DeSimone said.
Patients report having more energy when using the drug.
FUTURE RESEARCH: The next step of research, says DeSimone, is to do a longer study and to look at the drug in younger patients who have not experienced the organ damage that the older patients currently being studied are likely to have experienced.
"The idea is that if we can treat them early enough before they have major tissue damage, then maybe we can affect the progression of the tissue damage. The earlier we get to it, the better chance we have," said DeSimone.
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