Nov. 7, 2001 Researchers at Johns Hopkins Children's Center and 20 other hospitals report that a novel drug appears to make blood cells slip around each other and more easily through blood vessels, shortening the duration of painful crises experienced by children with sickle cell disease. The achievement represents a departure from the traditional approaches to controlling crises, which have focused on reducing misshapen cell counts and treating pain symptoms. The drug had a similar but less potent effect in adults.
The multicenter study, in this week's Journal of the American Medical Association, suggests PP-188 (purified poloxamer 188) decreases the viscosity of blood and its components, allowing even rigid, crescent-shaped sickle cells to move through narrow capillaries.
Sickle cell disease is caused by mutations in the genes for hemoglobin, an oxygen- carrying protein in red blood cells. The defective hemoglobin makes oxygen-poor red blood cells rigid and crescent-shaped (sickled). The sickled cells tend to clog small blood vessels, leading to painful crises. Sickle cell disease affects more than 50,000 Americans, especially blacks of West African descent, according to the National Institutes of Health.
"Current treatment after the onset of painful crises involves treating symptoms, but not really attacking the underlying cause," says pediatric hematologist James F. Casella, M.D., who oversaw Hopkins' contribution to the study. "There are no available drugs that have been proven to be effective in modifying the course of painful crises. PP-188 may be helpful in shortening crises and providing much-needed relief to patients."
Researchers enrolled 255 sickle cell disease patients in the study. All participants had sickle cell anemia or S-beta-thalassemia (a form of sickle cell disease), were between the ages of 9 and 53 years and were enrolled about 12 hours after they were admitted with crisis symptoms to hospitals or clinics. One hundred twenty-seven of the enrollees were randomly assigned to receive PP-188; the other 128 were given a placebo in a double blind trial. Researchers contacted patients periodically for at least 28 days after initial enrollment to determine their patients' crisis symptoms and duration.
Researchers found a nine-hour reduction of crisis time in patients who took PP-188 and a 16-hour reduction of crisis duration in those patients who were also taking hydroxyurea, a standard drug therapy that decreases the number of poorly formed red blood cells in the circulatory system. Even more noteworthy, Casella says, is the 21-hour reduction in crisis duration in children 15 years and younger.
"Our study supports the possibility that there is a fundamental difference in the way sickle cell disease manifests itself in children and adults," Casella says. "In adults, repeated tissue damage in the same place may result in a more chronic problem. If that's the case, this tissue damage may be reversible or preventable in children."
Researchers from the University of North Carolina at Chapel Hill; the University of Illinois at Chicago Medical Center; the University of Tennessee Medical Center; St. Louis Children's Hospital; the University of California at Davis School of Medicine; Children's Mercy Hospital in Kansas City, Mo.; St. Christopher's Hospital for Children in Philadelphia, Pa.; the Medical College of Georgia, Children's Healthcare of Atlanta, Ga.; the Medical University of South Carolina; the Boston University School of Medicine; the University of Alabama at Birmingham Medical Center; Harper Hospital in Detroit, Mich.; the Robert Wood Johnson Medical School; the Arkansas Children's Hospital; Jefferson Medical College, Colmar, Pa.; Theradex of Princeton, N.J.; and the CytRx corporation also contributed to the study. It was funded by a grant from the CytRx corporation.
Some study coauthors have received support from and/or have provided consultation advice to CytRx.
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