Stopping a Fatal Blood Disease in the Womb

Tippi MacKenzie, MD, is stopping disease before it starts – in the womb. In a first-of-its-kind clinical trial, she transplanted stem cells from an expectant mother to her own fetus to halt alpha thalassemia major (ATM), a potentially lethal disorder that can lead to progressive anemia and heart failure before birth.

Elianna, the first patient enrolled in the clinical trial, was born in February 2018. She had been critically ill during the second trimester of pregnancy and was delivered at 37 weeks weighing just under 5 pounds. She eventually returned with her family to their home in Hawaii. Her family celebrated her third birthday in February 2021.

“Elianna is doing very well, and her mom sends us lovely pictures all the time,” Dr. MacKenzie said in April 2021. “Since then, we have transplanted another two patients. The second patient, Milo, is now 2 years old, and the third has not been born yet.”

Currently, children with ATM face a lifetime of blood transfusions. For some newborns, a stem cell transplant with a matched donor can be a cure, but the procedure comes with a risk of rejection and serious side effects from immunosuppressive drugs. 

A transplantation in utero, on the other hand, takes advantage of the fetus’ nascent immune system. The mother’s cells flow freely through her fetus’ blood stream, so a fetus will not reject its mother’s stem cells, explains MacKenzie, a pediatric surgeon and co-director of the UCSF Center for Maternal-Fetal Precision Medicine. With a mother’s healthy cells, a fetus will have all it needs to produce blood cells of its own and avoid immunosuppressive drugs.

ATM was the ideal first candidate for a fetal infusion study because fetuses with the condition require continual blood transfusions. The maternal stem cells are infused at the same time, so no additional procedures are needed. UCSF brings an unrivaled expertise to the trial, which is underway at UCSF Benioff Children’s Hospitals in Oakland and San Francisco. UCSF Benioff Children’s Hospital Oakland has the largest thalassemia center in the country, and UCSF is the birthplace of fetal surgery.

Success in this study will open the door to exploring treatments for other life-threatening genetic blood diseases worldwide. MacKenzie said the trial is ongoing, and they plan to enroll 10 patients. In addition, she said, the Center for Maternal-Fetal Precision Medicine also produced a mini-documentary to tell the story of patients with this disease, including Elianna and Milo.

Dr. MacKenzie said the UCSF Benioff Children’s Hospitals Fetal Treatment Center is now launching a clinical trial of in utero enzyme replacement therapy in fetuses with certain lysomal storage diseases (LSDs), metabolic errors caused by a mutation coding for a crucial enzyme. Standard care for LSDs involves giving enzyme replacement therapy after birth; the clinical trial will examine the benefits of providing the therapy before birth.