Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe's disease favorably altered the natural history of the disease.
Transplantation in infants after symptoms had developed did not result in substantive neurologic improvement.
" 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 Maria Luisa Escolar, the study's lead author and at University of North Carolina ( UNC ) School of Medicine.
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 61⁄2 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.
The study also shows that newborns should be screened for Krabbe's disease, Kurtzberg said.
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.
Source: The New England Journal of Medicine, 2005