In a medical development with potentially far-reaching effects, researchers have transplanted cord blood into newborns with a rare genetic disease, preserving their brain development and performing a life-saving treatment for babies with a fatal genetic disorder.
Scientists from Duke University Medical Center and the University of North Carolina at Chapel Hill, infused cord blood stem cells after high-dose chemotherapy into a group of newborns with Krabbé disease, a condition in which children are missing an enzyme necessary to generate myelin, which insulates nerve cells and allows the transmission of nerve impulse.
In a study published in May in The New England Journal of Medicine, researchers said Krabbé patients — who had not yet developed symptoms but were treated after blood tests confirmed a diagnosis — showed age-appropriate developmental skills.
The treatment, researchers said, could be a precursor to therapy for other patients with metabolic disorders, including Tay-Sachs, for which several patients have undergone this same experimental treatment with varying success.
“It really opens the doors in terms of understanding other lysosomal diseases, and many of them have an effect on a nervous system and are deteriorating, like Krabbé disease,” said Dr. Maria Escolar, the lead author of the study. “We are trying to see if we can change the natural history of the disease.”
Since the first unrelated cord blood transplant was done in 1993, cord blood — harvested from the placenta or afterbirth — has most commonly been used to treat patients with leukemia, metabolic and bone marrow failure diseases.
With evidence that Krabbé patients benefited from bone marrow transplants, and knowing the disease presents itself in infancy, researchers were hopeful that cord blood would positively affect the babies.
To receive a cord blood transplant, patients first undergo chemotherapy to destroy their immune system and bone marrow, said Dr. Joanne Kurtzberg, director of the Duke pediatric blood and marrow transplant program. Then, cord blood is transfused and finds its way to the marrow where it repopulates the marrow and begins producing healthy cells, she said.
The healthy cells, which contain the enzyme Krabbé patients lack, circulate throughout the body and to the brain, replacing the missing enzyme and enabling the production of myelin.
With hospital stays, isolation to prevent infection and other health precautions during the first (and sometimes second) year of life, cord blood transplants are “not a simple procedure,” said Kurtzberg.
But the results in Krabbé patients are paying off. At least one patient who received a cord-blood transplant is in third grade and functions like a completely normal child, Kurtzberg said. “If you test him genetically, he still has the gene for the disease, but if you look at him functionally, he has no symptoms of the disease,” she said.
So far, the Duke-UNC team has transplanted 15 Krabbé newborns with cord blood, and all are in various stages of development, though they are following a similar course. Kurtzberg has transplanted 37 patients — some older — as well.
Six Tay-Sachs patients — two of them newborns at the time — have received cord-blood transplants. This has resulted in cognitive — but not motor — improvement.
“Certainly the jury is still out” for Tay-Sachs patients, said Jayne Gershkowitz director of the National Tay-Sachs & Allied Diseases Association. “Certainly this is showing great interest on the part of parents to see how this particular treatment will fare over time.”