Duke University, Durham, North Carolina, and the University of California, San Francisco are launching a new study to evaluate the maternal and fetal safety of in utero enzyme replacement therapy (ERT) in fetuses with lysosomal acid lipase deficiency (LAL-D) and other lysosomal storage diseases (LSDs).
LAL-D is a rare genetic autosomal recessive disorder of metabolism characterized by the excess accumulation of lipids in the body due to the absence of specific enzymes that normally break down these lipids. Mutations in the LIPA gene result in a lack of enzymatic function, leading to the buildup of cholesteryl esters and triglycerides in the liver, spleen, and other organs.
Fetuses with LSDs are at a high risk of severe perinatal morbidity and mortality due to, among other complications, nonimmune hydrops fetalis. In utero ERT has the potential to significantly improve their outcomes. Previous studies have shown the gestational period to be an opportune time for immune stimuli to the fetus, which could result in a good response to ERT.
In utero ERT also has the potential to result in improved neurodevelopmental outcomes if, as researchers suspect, the therapy affects the development of the nervous system.
Read more about LAL-D therapies
This interventional study will enroll approximately 10 participants who have been prenatally diagnosed with an LSD and who will be treated with in utero ERT with laronidase at a dose dependent on the specific disease and enzyme being replaced, as well as on the current estimated weight of the fetus. The therapy will be repeated every 2 to 4 weeks.
The open-label study is currently recruiting. Its start date was July 1, 2021, and the estimated primary completion date is July 2031. The final completion date is estimated to be July 2032.
In utero enzyme replacement therapy for lysosomal storage diseases (IUERT). ClinicalTrials.gov. August 31, 2020. Updated September 21, 2022. Accessed December 29, 2022.