Sickle Cell Anemia : Hydroxyurea Studies, Part 2, Inheritance

by Food and Drug Administration (FDA)

(Page 3 of 3)

Many questions about hydroxyurea in the treatment of sickle cell anemia remain unanswered, said Bonds. Doctors do not know what the most effective and least toxic dose of the drug is or whether taking it for many years presents health risks.

Some doctors prescribe hydroxyurea to treat polycythemia vera, a disease in which the number of red blood cells increases abnormally. Some evidence suggests that the drug may cause leukemia in a few of these patients, Bonds said.

However, he adds, patients with polycythemia vera already have a higher-than-average risk of getting leukemia, so it is unclear whether the leukemia is caused by hydroxyurea or whether the patients would have developed it anyway.

NHLBI is conducting a five-year follow-up study of patients who took part in the hydroxyurea trial to see whether any of them develop leukemia or other problems that may result from long-term use of the drug. Another study, which began in January 1995, is looking at the safety and effectiveness of hydroxyurea in children ages 5 to 15 who have sickle cell anemia.

Research continues on other possible ways of reducing the occurrence of painful sickle cell episodes by increasing the production of fetal hemoglobin. For example, NIH scientists are studying whether a combined regimen of hydroxyurea and erythropoietin, a hormone that increases the production of red blood cells, is less toxic and more effective than Hydrea alone. (Erythropoietin is licensed by FDA to treat anemia in certain patients.) Studies are also under way to determine the safety and efficacy of butyrate, an experimental drug that can stimulate production of fetal hemoglobin.

NHLBI recently funded three centers that will try to develop gene therapy for sickle cell anemia, said Bonds. "If you could replace the abnormal genes, you could cure the disease. However, there are significant technical problems involved in making gene therapy work."

Because of these problems, gene therapy is unlikely to be a reality for many years, she said. Nevertheless, she said she is optimistic that new, effective treatments for sickle cell anemia will be developed in the future.

"I like to tell people that [the results of the hydroxyurea study] will one day be likened to [the discovery of] insulin or penicillin. Those drugs were the first major breakthroughs for the treatment of diabetes and severe bacterial infections, although other agents have since [been introduced] to treat those diseases."

Sickle Cell Inheritance

In the United States, sickle cell anemia is most common among African Americans. Every year, about 1 in 400 African-American infants is born with the disease after inheriting the genetic mutation from both parents.

People who have only one copy of the mutation are said to have sickle cell trait. It is estimated that 1 in 12 African Americans has sickle cell trait. People with sickle cell trait are usually healthy, although they can pass the mutation on to their children.

A child conceived by two people with sickle cell trait has one chance in two of also having sickle cell trait, one chance in four of having sickle cell anemia, and one chance in four of inheriting neither the trait nor the disease, according to Lilia Talarico, M.D., director of the division of gastrointestinal and hematologic drug products in FDA's Center for Drug Evaluation and Research.

Genetic counseling may be useful to patients with sickle cell traits or disease. And prenatal diagnosis of sickle cell anemia is possible.

The disease can also occur among non-African Americans. "People whose ancestors came from parts of the world where malaria was prevalent are potentially carriers of the sickle gene," said Duane R. Bonds, M.D., of the National Heart, Lung, and Blood Institute. "In addition to people of African descent, people whose ancestors came from the Mediterranean basin-Greece, Italy, Sardinia-may also carry the gene. The sickle gene is also found in parts of India and the Arabian peninsula."

In the past, individuals with sickle cell anemia often died in childhood. A 1973 study estimated that half of those with the disease died by the age of 14. A frequent cause of death was bacterial infection by the organism Streptococcus pneumoniae. Children with sickle cell anemia are highly susceptible to infections because they lose the function of their spleen, which provides protection against bacterial infections.

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