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Prenatal Enzyme Replacement Therapy for Lysosomal Storage Diseases

Prenatal Enzyme Replacement Therapy (ERT) for Fetuses with Lysosomal Storage Diseases: An International Phase 1 Clinical Trial

Pregnant patients with a diagnosed fetal lysosomal storage disease may have the opportunity to receive a promising treatment that could improve their babies’ health after birth. UCSF has received FDA approval to treat eight lysosomal storage diseases with enzyme replacement therapy prenatally for a Phase 1 clinical trial of 10 patients.

Standard care for these diseases involves giving enzyme replacement therapy (ERT) after birth. The potential benefits of giving ERT before birth include preventing organ damage from storage that may occur in the fetal period. Additionally, enzyme therapy given before birth can cross into the brain because of the fetus’ developing blood brain barrier. Giving ERT before birth may prevent or slow the progression of the disease on the brain. Finally, the exposure to enzyme before birth may prevent the development of antibodies and/or an allergic reaction to the medicine when given after birth.

The diseases being treated are Mucopolysaccharidosis types 1, 2, 4a, 6 and 7; Gaucher disease types 2 and 3; Infantile-onset Pompe disease (IOPD), and Wolman disease. The researchers hope the success of this first application and publication of the case study will increase awareness of the ongoing clinical trial among parents at known risk of passing on these diseases and the physicians who treat them.

UCSF Health’s Deparment of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, working in tandem with UCSF’s Fetal Treatment Center, continues to enroll women with a fetus diagnosed with one of eight lysosomal storage diseases, after confirmation from prenatal diagnosis. Between 18 to 35 weeks’ gestation, UCSF perinatologist and maternal-fetal medicine specialist, Juan Gonzalez-Velez, MD, will give the weight-based dose of the relevant FDA-approved enzyme replacement therapy every 2-4 weeks. This will be done by an umbilical vein injection, a procedure routinely used for in utero blood transfusions, and that has a good safety profile. After birth, the baby will receive standard care, including ERT and possibly stem cell transplantation (depending on the disease). UCSF will follow the child for 5 years after birth, to determine whether prenatal ERT improves long-term outcomes such as neurologic function, mobility, and growth.

The PEARL Trial team has funding to cover participant costs related to travel and research-related procedures. Some procedures are standard of care and will be billed to participant insurance. The study team will facilitate a virtual call with prospective patients prior to travel for enrollment evaluation to ensure they understand the details of the study and the expectations for participation.

Already, the prenatal therapy developed at UCSF was used to successfully treat a fetus with infantile-onset Pompe disease, a rare and fatal genetic disorder that affects multiple organs. The baby, now one year old, is thriving, and published results were reported in the New England Journal of Medicine.

Tippi C. MacKenzie, MD, is the study’s principal investigator and co-director of the Center for Maternal-Fetal Precision Medicine.

Refer to Fetal Treatment Center