Sickle Cell Disease - Treatment

Hydroxyurea is still being investigated in young people. To date, the response to the drug in children and teenagers with sickle cell disease is similar to the response in adults, and few severe adverse effects are being reported. Recent research also suggests that hyrdoxyurea is safe and beneficial for infants. A 2005 study indicated that long-term hydroxyurea treatment can improve height, weight, and spleen function, and reduce episodes of acute chest syndrome. Patients in the study started the treatment as babies, and most patients took the drug for at least 4 years. The drug was given by mouth in a flavored liquid form.

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Side effects include gastrointestinal problems, headache, drowsiness, and skin and nail changes. In rare cases, there have been reports of hallucinations and seizures. Long-term use of hydroxyurea (three years) may induce leg ulcers in certain patients. There is some concern that it may also pose a slight long-term risk for cancers, such as leukemia, but long-term research is needed. At this time, it should not be used during pregnancy.

Cytidine Analogues.Cytidine analogues increase HbF production by affecting the genes that regulate it. Decitabine is one such drug that was developed to treat leukemia and other blood malignancies. Early studies are suggesting that it significantly increases HbF production, even in patients who have failed hydroxyurea. Only minor toxic side effects have been reported to date.

Butyrates.Butyrates are natural fatty acids, which are the end-products of fermented carbohydrates in the intestinal tract and they are also metabolized from fiber. One derivative, arginine butyrate, has been under investigation for some time in sickle cell for its role in stimulating production of HbF. Intermittent therapy using intravenous administration has achieved increased levels. In a promising 2002 study administering arginine butyrate improved ulcer healing by ten-fold. Because its actions are different from hydroxyurea, experts hope the two drugs may eventually be used in combination. However, arginine butyrate is difficult to administer, and experts are looking for different forms that might make it simpler to use.

Nitric Oxide and Arginine

Nitric oxide, a soluble gas, is a natural chemical in the body that relaxes smooth muscles and expands blood vessels. Hemoglobin removes nitric oxide. Because sickle cells release hemoglobin, patients with the disease are deficient in nitric oxide. This lack of nitric oxide constricts blood vessels and causes pain in sickle cell diseases. In adult patients, men may be more susceptible to this effect than women. Some studies indicate that inhaling nitric oxide may slow the disease process and improve symptoms in acute sickle cell crises. It is difficult to administer, however. (Nitric oxide is not the same substance as nitrous oxide, the so-called laughing gas used in dentistry.)