The first birth from a groundbreaking trial of in utero stem cell transplantation suggests that fetal therapy may be a viable new option for alpha thalassemia (ATM). Some 5% of the world’s population carries the gene for ATM, which is almost universally fatal in utero because of a lack of effective therapies.
The delivery at 37 weeks’ gestation, which occurred in February at UCSF, was recently announced by researchers there who are conducting a phase 1 clinical trial to demonstrate the safety, feasibility, and efficacy of performing in utero stem cell transplantation (SCT) on fetuses affected with ATM. The infant’s mother is the first of 10 participants with a prenatal diagnosis of ATM to be recruited and she and her husband are carriers of the ATM gene.
Prior to the transplant, intrauterine transfusions (IUT) were performed to treat the fetus’s hydrops. For the transplant, the mother’s bone marrow was harvested, hematopoietic stem cells (HSC) were extracted, and they were administered to the fetus as part of a transfusion. HSC transplantation into the fetus takes advantage of the developing fetal immune system to induce tolerance to the transplanted cells without using conditioning or immunosuppression. Performing SCT at the same time as IUT minimizes any additional procedural risk to the fetus.
The infant has been discharged from the hospital and investigators said she will require further blood transfusions or another SCT to remain healthy. The trial is the first of in utero SCT and besides demonstrating the technique’s safety and feasibility, the researchers also want to demonstrate postnatal chimerism of maternal cells so that, if an infant requires bone marrow transplant after delivery, no conditioning or immune suppression will be needed.