Every baby should be tested for sickle cell disease, and thoseafflicted should receive penicillin twice a day until the age of 5to prevent life-threatening illnesses.
This is the gist of a guideline issued Tuesday by the Agency forHealth Care Policy and Research of the U.S. Public HealthService.
Meanwhile, a number of researchers and at least one company,Genetix Pharmaceuticals Inc. of Tarrytown, N.Y., are working ondeveloping gene therapy for the disease.
In the U.S., one out of every 375 African-Americans carries thesickle cell trait. But Italians, Greeks, Saudi Arabians, Caribbeanpeople of Hispanic heritage, and people from the Indiansubcontinent sometimes carry the trait, Thomas Kinney,professor of pediatrics at Duke University School of Medicineand co-author of the guideline, told BioWorld.
Screening all babies is desirable because "it is impossible to tellsomebody's racial background by their physical appearancewith 100 percent accuracy," said Kinney, and because "failureto identify these babies really puts them at risk of death fromoverwhelming infections," chiefly pneumonia and meningitis.
"Historically, the mortality rate has been 15 to 20 percentwithin the first three years," said Kinney. Studies have shownunequivocally that prophylactic penicillin will prevent thosedeaths in children up to age 5.
As for gene therapy, "the obstacles are mainly technical, andnot theoretical," said Arthur Bank, professor of medicine andgenetics at Columbia University College of Physicians andSurgeons. Transferring the gene has proven difficult, andexpression has rarely exceeded 10 percent, which is too low totreat hemoglobinopathies.
Bank thinks that certain structures in the DNA may blocktransfer and expression. "Many labs, including my own, areattempting to delete certain regions of the globin genes andretroviral vectors that may be interfering with the properexpression of the genes."
But if a gene, such as the multiple drug resistance (MDR) geneis inserted successfully, "that gene will be retained andexpressed up to 10 months after bone marrow transplantation."Bank said he expects to see the technology succeed for globingenes in humans within the next few years.
Genetix is approaching gene therapy for hemoglobinopathies inwhat might appear to be a roundabout way. At the nextmeeting of the Recombinant DNA Advisory Committee of theNational Institutes of Health, the company will requestpermission to insert the MDR gene into bone marrow stem cellsof cancer patients. The gene encodes a glycoprotein that pumpscertain chemotherapeutic agents out of the cells, which wouldallow doctors to raise the dose of chemotherapy.
For hemoglobinopathies, insertion of the chemotherapy-resistant MDR gene with the normal hemoglobin gene offers away around the problem of low expression, said Ronald Dorazio,vice president of Genetix and a company founder. Stem cellsthat had not been transduced could be killed off with a mildchemotherapy agent, eliminating the bad blood.
Another way to treat hemoglobinopathies, including sickle celldisease, is to increase production of fetal hemoglobin. Thisreduces formation of the sickle-shaped red blood cells.Compounds such as butyrate and hydroxyurea have shownpromise, but researchers are also trying biotechnologicalapproaches.
Bank's laboratory has located a factor that is present only inadult red blood cells, which he thinks may block fetal genesand stimulate production of adult hemoglobin.
"Something that sopped up this factor might cause stem cells torevert to production of fetal hemoglobin," he said. "Ourpreliminary results are encouraging."
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.