Umbilical cord-blood transplants save lives of babies with rare genetic disorder

Umbilical cord-blood transplants save the lives of newborns with a rare genetic disorder called Krabbe’s disease and helps their brains develop more normally, a study led by researchers at the University of North Carolina at Chapel Hill and Duke University Medical Center concludes.

“Infants with Krabbe Disease lack an enzyme necessary for normal myelination of the brain and peripheral nervous system at the time when myelination is occuring most rapidly. The infants become irritable, loose all their developmental skills, become deaf and blind, have seizures and die. It is very painful for parents to watch their children deteriorate this rapidly. This study shows that finally there’s a treatment that offers hope,” said Dr. Maria Luisa Escolar, the study’s lead author.

Escolar is an assistant professor in the UNC School of Medicine’s department of pediatrics. She also is director of the Program for Neurodevelopmental Function in Rare Disorders, part of UNC’s Clinical Center for the Study of Development & Learning. This program is dedicated to longitudinally track neurological and functional changes in patients with rare diseases. With a database of more than 450 multidisciplinary evaluations the program’s main goal is to describe the natural history of rare diseases and the effects of new treatments.

Results of the study will be published in the May 19 issue of the New England Journal of Medicine. The study’s senior author is Dr. Joanne Kurtzberg, director of Duke’s Pediatric Blood and Marrow Transplant Program.

The study demonstrates that umbilical cord-blood transplant is a life-saving treatment for newborns with infantile Krabbe’s disease, an inherited degenerative disorder that affects the nervous system, said Kurtzberg. Most infants with the disease die before reaching age 2. In addition, Kurtzberg added, the study adds to a growing body of evidence that cord blood can save children with other “lysosomal storage diseases.” These include more than 45 diseases, such as Krabbe’s disease, Hurler syndrome, Adrenoleukodystrophy, metachromatic leukodystrophy, Tay-Sachs disease, Sandhoff disease and a host of others.

All the infants in the study who received cord-blood transplants as newborns are still alive, with the oldest being 6½ years old, up to four years after an untreated sibling with the same disorder had died. Moreover, most newborns who were treated before the onset of symptoms showed continual improvement in developmental skills and had age-appropriate mental and language skills.

“Time is of the essence in treating the children before symptoms progress and become irreversible,” said Kurtzberg. “The diseases may be uncommon, but the cost to the child, their family and to society at large is enormous when one considers the burden of caring for a severely disabled child. It’s simply impossible to put a price on a child’s life.”

The study also shows that newborns should be screened for Krabbe’s disease, Kurtzberg said. In current practice, they are not.

Dr. Mel Levine, director of UNC’s Clinical Center for the Study of Development & Learning, said Escolar and her colleagues are breaking new ground in uncovering the inborn lesions that impede learning and development in certain children. “Their research has lead to miraculous innovative interventions that can serve as a model for preventing the progression of brain damage in vulnerable babies and preschoolers,” he added.

Worldwide, infantile Krabbe’s disease occurs in about one in 100,000 births. It is caused by a deficiency of the enzyme galactocerebrosidase, or GALC, which leads to a loss of myelin, a fatty covering that wraps around and protects nerve fibers in the brain. Without myelin, nerves in the brain and other parts of the body cannot function properly.

Previous studies have shown that individuals with late onset Krabbe’s disease benefited when transplanted with stem cells taken from bone marrow. However, banked umbilical-cord blood is much more readily available than bone marrow and can be used for infant stem cell transplants after they have been treated with chemotherapy.

In the study, 11 newborns diagnosed with Krabbe’s disease but showing no symptoms and 14 older infants with symptoms underwent transplantation of umbilical-cord blood from unrelated donors following chemotherapy. These infants were then evaluated periodically for up to six years.

Twenty-two of the 25 infants received cord-blood transplants at Duke University Medical Center; the other three were transplanted at hospitals in St. Louis; Grand Rapids, Mich.; and Montreal. Escolar analyzed the developmental trajectory of all infants and conducted pre and post transplant developmental evaluations in 10 newborns and all of the symptomatic patients that survived.

As of January 2005, all 11 newborns had survived for a median of 36 months, while six of the 14 symptomatic infants had survived for a median of 41 months. The survival rate among the newborns was better than among untreated control patients and the symptomatic infants. In addition, six of the newborns outlived their affected siblings by eight to 48 months.

Escolar demonstrates that the newborns had better neurological outcomes than both untreated infants and infants treated after the onset of symptoms. The newborns maintained normal vision and hearing and normal cognitive development, except for areas influenced by gross motor development. In contrast, the infants treated after symptom onset showed some stabilization of neurologic disease, but remained severely impaired.