Infants with Rare Genetic Disease Saved By Cord Blood Stem Cells
DURHAM, N.C. -- Children with a fatal genetic disorder
called Krabbe Disease can be saved and their brain development
preserved if they receive stem cells from umbilical cord blood
before symptoms of the disease develop, according to a study
published in the May 19, 2005, issue of the New England Journal
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
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
"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
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
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
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
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.