Infants With Rare Genetic Disease Saved By Cord Blood Stem Cells

Without an immediate transplant of stem cells, Krabbe infants rapidly begin to lose all cognitive and motor functions and die by the age of two, said the researchers. They are from Duke University Medical Center's Pediatric Blood and Marrow Transplant Program and The Clinical Center for the Study of Development & Learning at the University of North Carolina at Chapel Hill (UNC-CH).

The study is the first to demonstrate a life-saving treatment for newborns with Krabbe Disease, in which children are missing an enzyme critical to forming the myelin sheath that protects developing brain cells from damage. Moreover, the findings add to the growing body of evidence showing that cord blood can save children with other fatal "lysosomal storage diseases," each of which stems from a specific enzyme deficiency.

These disorders include more than 45 rare diseases, such as Krabbe disease, Hurler syndrome, Adrenoleukodystrophy, Metachromatic Leukodystrophy, Tay-Sachs disease, Sandhoff disease and a host of others.

"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," said Joanne Kurtzberg, senior author of the study. "It's simply impossible to put a price on a child's life."

Kurtzberg pioneered the use of umbilical cord blood from unrelated donors in 1993 and her team has treated and saved more children with cancers and rare genetic diseases than any other center in the world -- 147 children in all. The oldest Duke patient transplanted for a lysosomal storage disease is now seven years old and has developed and progressed normally, according to Kurtzberg.

Kurtzberg said their treatment successes provide a strong argument for mandatory, universal screening of all newborns for the genetic lysosomal storage diseases. The major barrier to universal newborn screening is building an infrastructure to support widespread testing, she said. The cost of testing itself would be relatively low.

Although lysosomal storage diseases are rare -- fewer than 5,000 births combined out of 4 million per year in the U.S. -- they are best treated if patients are diagnosed and treated in early infancy, said Kurtzberg. In fact, transplantation in newborns yields the best long-term outcomes and newborns tolerate the transplants more easily than older babies and children.

"Time is of the essence in treating these children before symptoms progress and become irreversible," said Kurtzberg, director of Duke's Pediatric Blood and Marrow Transplant Program. "Delaying the transplant even a week or two can make a noticeable difference in a child's motor skills, so timely diagnosis and treatment is essential to preserving brain and motor function."

Children transplanted after onset of symptoms do stabilize but exhibit minimal neurologic improvement, said Maria Luisa Escolar, MD, of UNC-CH, whose team assessed the neurological, cognitive and physical development of each child with Krabbe Disease before and after transplant.

Escolar is lead author of the study and directs the Program for Neurodevelopmental Function in Rare Disorders at the Center for Development and Learning, UNC-CH. The program is dedicated to tracking the natural history and the effects of new therapies in children with rare diseases.

In the new study, eleven asymptomatic newborns (ages 12 to 44 days) and 14 symptomatic infants (ages 142 days to a year) were treated with unrelated donor umbilical cord blood. Cells from the donor "engrafted" or took hold in all of the patients. All of the asymptomatic newborns survived transplant, whereas only 43 percent of the symptomatic babies survived, the study showed.

While the child's age and symptom severity at the time of transplant are crucial to determining outcome, the source of stem cells is also important, said Kurtzberg.

Cord blood appears to provide a better and faster correction of enzyme deficiencies than does adult bone marrow, she said. Stem cells from cord blood travel to the brain more rapidly than stem cells from adult bone marrow, and cord blood stem cells repair deficiencies in both the central and peripheral nervous systems, said Kurtzberg.

Thus, disease progression stabilizes about 2 to 4 months earlier in patients who receive cord blood compared to those who receive adult bone marrow, and huge developmental milestones occur during that period of infancy, said Kurtzberg.

The ease of obtaining cord blood also makes it an excellent source of stem cells, she said. Cord blood is readily available because it is extracted from discarded placentas (afterbirth) following child birth. Adult bone marrow must be harvested from living donors through an invasive surgical procedure.

Finally, cord blood cells are less mature than adult bone marrow cells and thus do not need to perfectly match the patient's immune-related blood proteins, called antigens, said Kurtzberg. Only four of six cord blood "antigens" must match for a transplant to have a reasonable chance of success, whereas adult bone marrow requires a greater degree of matching antigens, she said.

As a result, a cord blood donor unit can be identified and obtained within a week, whereas a matching adult donor can takes months to locate and obtain if available at all, said Kurtzberg.

Similar benefits of cord blood were seen in an earlier Duke study of children with Hurler Syndrome, results of which were published in the May 6, 2004, issue of the New England Journal of Medicine. In that study, Kurtzberg's team demonstrated that 85 percent of children who received cord blood survived for two to seven years -- the longest period of time they have been followed. Survival among Hurler's children who receive bone marrow is between 63 and 72 percent.