Umbilical cord blood successfully treats rare genetic disorders
Researchers at UPMC Children's Hospital of
Pittsburgh found that infusing umbilical cord blood -- a readily available source of stem cells -- safely and effectively
treated 44 children born with various non-cancerous genetic disorders,
including sickle cell, thalassemia, Hunter syndrome, Krabbe disease,
metachromatic leukodystrophy (MLD) and an array of immune deficiencies. This is
the largest trial of its kind to date.
The idea was to create a fairly
universal treatment, rather than chasing individual therapies for all of these
rare diseases, and to do so with minimal risk to the patients. The results were
published in today's print edition of Blood Advances.
The
idea was to create a fairly universal treatment, rather than chasing individual
therapies for all of these rare diseases, and to do so with minimal risk to the
patients. The results were published in today's print edition of Blood
Advances.
"There
has been a lot of emphasis placed on cool new technologies that might address
these diseases, but -- even if they prove effective -- those aren't available
to most centers," said study senior author Paul Szabolcs, M.D., division
director of bone marrow transplantation and cellular therapies at UPMC
Children's Hospital. "The regimen we developed is more robust, readily
applicable and will remain significantly less expensive."
For this
study, the participants received intravenous injections of banked cord blood,
which was donated from the umbilical cords and placentas of healthy babies just
after birth and frozen until needed.
To
make room in their bone marrow for donor stem cells to take root and prevent
them from being rejected, study participants received a low dose of
chemotherapy and immunosuppressant drugs in a careful sequence. Once the cells
integrated into the patients' bodies, these drugs were tapered off. To kick the
immune system back into gear, the researchers reserved a small fraction of the
cord blood and gave it to participants a few weeks after the initial infusion.
It's important to note that this procedure doesn't require the donor and recipient to have matching immune profiles.
It's important to note that this procedure doesn't require the donor and recipient to have matching immune profiles.
"That is
huge for ethnic minorities," Szabolcs said. "The probability of a
perfect match is very low, but with a cord blood graft, we have a chance to
overcome this discrepancy over the course of a couple months and then taper
immunosuppressants away."
Overall, post-infusion complications were
relatively mild. None of the participants experienced severe chronic
graft-versus-host disease, and the mortality rate from viral infection due to
immune suppression was 5%, which is much lower than in prior studies.
For the 30 children in the trial with metabolic disorders -- in which improper enzyme function causes the buildup of harmful toxins in the body -- all but one exhibited progressive symptoms of neurodevelopmental delays before the start of the trial. Within a year of receiving cord blood, all of them had normal enzyme levels, and all showed a halting of neurological decline. Some even began to gain new skills.
For the 30 children in the trial with metabolic disorders -- in which improper enzyme function causes the buildup of harmful toxins in the body -- all but one exhibited progressive symptoms of neurodevelopmental delays before the start of the trial. Within a year of receiving cord blood, all of them had normal enzyme levels, and all showed a halting of neurological decline. Some even began to gain new skills.
The most common metabolic disorders in this
study were leukodystrophies, which typically are fatal within a few years of
symptom onset. Even with cord blood treatment, a large retrospective analysis
reported a three-year survival rate of about 60%. With the protocol used in
this study, more than 90% of symptomatic leukodystrophy patients were still
alive three years after their cord blood treatment.
No
previous studies using stem cells to treat metabolic, immune or blood disorders
have shown such high levels of safety, efficacy or broad applicability.
"There
has been a stagnation of outcomes in this field, just changing one chemotherapy
agent for another, not a true evolution," Szabolcs said. "We designed
an approach now proven to be efficacious for at least 20 diseases. And we
believe it might be effective for many, many more."
Since this
paper was submitted, the researchers already have had success with using this
technique to treat additional diseases, including in adults.