Hurler’s syndrome is a rare hereditary condition caused by the lack of an enzyme needed to regulate basic cell functions. Treatments to replace the enzyme help children with the condition but don’t salvage cells in all parts of the body.
Bone marrow transplantation, which supplies a child with new cells that can make the enzyme, has been the only way to cure Hurler’s syndrome. But unless a child has a closely matching marrow donor, such transplants often introduce severe complications.
In recent years, doctors have started giving Hurler’s babies infusions of donated umbilical cord blood as a way to provide enzyme-making cells. In the first study to analyze this practice over several years, scientists report success—a high survival rate, manageable side effects, and a general reversal of Hurler’s syndrome in most babies getting the treatment. The findings appear in the May 6 New England Journal of Medicine.
If both parents carry a mutation in the gene that underlies Hurler’s syndrome, a child has a 1-in-4 chance of getting two defective gene copies. The result is a lack of the enzyme alpha-L-iduronidase. Without it, sugar molecules accumulate in cells, causing irreversible tissue damage. Hurler’s syndrome is marked by mental retardation, stunted growth, and heart problems. Untreated children usually die by age 10.
Infusions of manufactured alpha-L-iduronidase can ameliorate some symptoms but probably don’t penetrate the blood-brain barrier and therefore don’t prevent brain damage, says study coauthor Joanne Kurtzberg, a pediatric oncologist at Duke University Medical Center in Durham, N.C.
Bone marrow and cord blood both contain various stem cells that develop into producers of alpha-L-iduronidase. After a bone marrow or cord-blood transplant, these cells, which include nascent white blood cells and brain cells called oligodendrocytes, appear to mature in the recipients, Kurtzberg says.
Researchers at Duke gave cord-blood infusions to 20 babies or toddlers diagnosed with Hurler’s syndrome during a 7-year period. The donors weren’t relatives of the babies. The babies had first received chemotherapy to wipe out their own defective bone marrow.
Of the six immune system proteins that doctors use as guideposts to match donors with recipients, only one Hurler’s baby had a six-out-of-six match with the cord-blood donor. Eleven babies had a five-out-of-six match, and eight babies had matches in only three or four of the proteins.
Nevertheless, 17 of the 20 babies survived their transplants and are still alive, Kurtzberg says. The oldest is now 7 years old. All the babies experienced some graft-versus-host disease, in which immune cells in the cord blood attack the recipient. But this complication was largely limited to temporary skin rashes.
Notably, the surviving cord-blood recipients are showing stabilized or improved brain development. All those who are old enough are attending school in the grade appropriate for their age, Kurtzberg says.
More than 200 Hurler’s babies have successfully received bone marrow transplants since 1980. However, finding a closely matched marrow donor remains difficult, says Joseph Muenzer, a pediatrician and geneticist at the University of North Carolina at Chapel Hill.
“With cord blood, [doctors] can use a partial match,” he notes. “That’s probably the big plus.” Still, it’s too early to say whether cord blood will be a more valuable treatment than bone marrow transplants for Hurler’s patients, Muenzer concludes.