- The race for a universal treatment of rare genetic diseases, has been on for many years now
- The new treatment regimen uses banked cord blood from the umbilical cord and placentas of healthy babies, that are frozen immediately after birth
- This treatment protocol is robust, readily applicable, less expensive and poses minimal risk to the patient
Non-malignant genetic disorders like sickle cell, thalassemia, Hunter syndrome, Krabbe disease, metachromatic leukodystrophy (MLD), and many such immune deficiencies can be cured or improved by umbilical cord blood infusion in children. Umbilical cord blood is a readily available source of stem cells.
Cord blood infusion from a healthy donor can decrease the severity of the illness in many nonmalignant disorders (NMDs), including primary immunodeficiency diseases, hemoglobinopathies, bone marrow failure syndromes, and inborn errors of metabolism (IEM). The therapy helps by replacing defective red blood cells, or leukocytes, or by releasing missing enzymes in the case of metabolic disorders.
Researchers at the UPMC Children's Hospital of Pittsburgh found that infusing umbilical cord blood safely and effectively treated children born with various non-cancerous genetic disorders. This is the largest trial of its kind to date and the results are published in Blood Advances.
Senior author Paul Szabolcs states that "There has been a lot of emphases placed on cool new technologies that might address these diseases, but -- even if they prove effective -- those aren't available to most centers. The regimen we developed is more robust, readily applicable, and will remain significantly less expensive."
The study participants included 44 children with various non-malignant genetic disorders. The children received two infusions of banked cord blood via intravenous injections. The banked cord blood was donated from the umbilical cords and placentas of healthy babies just after birth and frozen.
The participants received a low dose of chemotherapy and immunosuppressant drugs to prevent the rejection of donor stem cells and make room for bone marrow for donor stem cells to take root. They were weaned off from the drugs, once the cells integrated into the patients' bodies.
A second infusion was given a few weeks after the initial infusion. The procedure does not require compatibility in the immune profiles of the donor and recipient.
"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."
The rate of post-infusion infections and complications was low. The mortality rate from viral infections due to immune suppression was only 5%. None of the participants experienced severe chronic graft-versus-host disease.
Neurodevelopmental delays are common in metabolic syndrome. Metabolic syndrome leads to the accumulation of harmful toxins in the body due to improper enzyme function.
Among the 44 children, 30 children had metabolic disorders with progressive symptoms of neurodevelopmental delays before the trial. But within a year of receiving cord blood infusion, the enzyme levels returned to normal, and there was a halting of neurodevelopmental decline. Some of the children also began to acquire new skills.
The most common metabolic syndrome is leukodystrophy, which is fatal within the first few years of symptoms onset. Previous studies using cord blood treatment showed a three-year survival rate of about 60%. The three-year survival rate, using this study protocol, was about 90% in symptomatic leukodystrophy patients.
This is the first study to use stem cells to treat metabolic, immune, or blood disorders and to show a higher level of efficacy and safety. It also has broad applicability covering at least 20 diseases.
"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."
The therapy using cord blood cells has shown success in treating additional diseases, including in adults.