RARE Daily

Researchers Successfully Treat Range of Rare Genetic Disorders with Cord Blood

July 14, 2020

Infusing umbilical cord blood, a readily available source of stem cells, safely and effectively treated 44 children born with various non-cancerous genetic disorders, researchers at UPMC Children’s Hospital of Pittsburgh report.

The conditions treated included sickle cell, thalassemia, Hunter syndrome, Krabbe disease, metachromatic leukodystrophy, and a range of immune deficiencies.

The study, the largest trial of its kind to date, sought to create a universal treatment, rather than pursuing individual therapies for a range of rare diseases, while minimizing risks to patients. The results were published in 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, division director of the 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.”

Participants in the study 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.

Study participants received a low dose of chemotherapy and immunosuppressant drugs in a careful sequence to create room in their bone marrow for donor stem cells to take root and prevent them from being rejected. Once the cells integrated into the patients’ bodies, patients were tapered off the drugs. 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.

One benefit of this approach, the researchers note, is that the procedure doesn’t require the donor and recipient to have matching immune profiles.

“That’s 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 percent, which is 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.

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 percent. With the protocol used in this study, more than 90 percent 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 report that they already have had success with using this technique to treat additional diseases, including in adults.

Photo: Paul Szabolcs, division director of the Bone Marrow Transplantation and Cellular Therapies, UPMC Children’s Hospital.  Credit: UPMC

Author: Rare Daily Staff

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