Clinical Trials

PRENATAL ENZYME REPLACEMENT THERAPY RESEARCH STUDY IS ENROLLING FOR PREGNANCIES AFFECTED WITH RAPIDLY PROGRESSIVE INFANTILE LALD (WOLMAN DISEASE).  

Lysosomal storage conditions can be more severe and rapidly progressive or more slowly progressive, depending on the amount of proper protein functioning. In severe infantile lysosomal acid lipase deficiency patients (Wolman disease), there is little or no enzyme activity, and babies may look normal at birth, but there is already severe accumulation of lipids in most cell types with damage to multiple organs. One challenge of enzyme therapy is that although it is possible to reverse disease symptoms, it is most effective at preventing disease progression. If there is too much damage to a cell, the damage may be irreversible. Another challenge is that babies who produce essentially no enzyme are more likely to launch an immune response against enzyme replacement therapy, requiring immune suppression, or sometimes making it impossible for a baby to tolerate the treatment. This is why some infants do not respond as well to enzyme replacement therapy as others.

Researchers at University of California, San Francisco and Duke University Medical Center are investigating enzyme replacement therapy infusions delivered during pregnancy through the umbilical vein. The preclinical studies were successful, and the outcome of the first prenatal patient to receive enzyme replacement therapy during pregnancy was presented at the LDN WorldSymposium last February. The patient had a condition called Pompe disease, a lysosomal storage disorder resulting in glycogen build up in the cells, which causes severe heart, lung and muscle damage and death in the first one or two years of life. The treatment was started at 24 weeks of pregnancy, and the baby was healthy at birth. Most babies with no enzyme activity, including the patient’s sibling, are born with severe heart problems and cannot move because of too much glycogen in the muscles.

Enzyme replacement therapy during pregnancy is being offered on a research basis for families with a fetus diagnosed with rapidly progressive, infantile LALD. If there are any families who have a pregnancy affected with infantile LALD (Wolman disease) or if you would like to know more about the study please visit

PEARL Prenatal Enzyme Replacement Therapy for Lysosomal Storage Disorders Information Link

or email me at DonnaLBernstein@LALDAware.Org

The Lysosomal Acid Lipase Deficiency Registry

The LAL-D Registry is a place where your doctor can enter information about LAL-D patients’ medical condition but with no identifying information. This is essential, especially since LAL-D is rare because it helps researchers to learn more about the characteristics of LAL-D to increase scientific knowledge and lead to new discoveries. Please ask your doctor if you would like to be enrolled in the LAL-D registry so that your signs and symptoms or your child’s can be including in the body of knowledge on LAL-D.

To learn more about the LAL-D Registry, please visit LALD Registry ClinicalTrials.Gov Information Link

Lysosomal Acid Lipase (LAL) Deficiency Registry (ALX-LALD-501)

ClinicalTrials.gov ID NCT01633489

Sponsor Alexion Pharmaceuticals, Inc.

Information provided by Alexion Pharmaceuticals, Inc. (Responsible Party)

Last Update Posted 2025-11-13

Brief Summary

This is an observational, multi-center, international disease registry designed to collect longitudinal data and create a knowledge base that will be utilized to improve the care and treatment of patients with LAL Deficiency. Participation in the Registry by both physicians and patients is voluntary.

A Registry from the University of California, San Francisco  is open to patients with LALD and other lysosomal storage conditions to collect information on the signs and symptoms of lysosomal storage conditions to learn about the effects of prenatal (also called in utero) enzyme replacement therapy.

Registry of Patients Diagnosed With Lysosomal Storage Diseases (LSD Registry)

ClinicalTrials.gov ID NCT05619900

Sponsor University of California, San Francisco

Information provided by University of California, San Francisco (Responsible Party)

Last Update Posted 2025-01-27

Brief Summary

This is an international prospective and retrospective registry of patients with Lysosomal Storage Diseases (LSDs) to understand the natural history of the disease and the outcomes of fetal therapies, with the overall goal of improving the prenatal management of patients with LSDs.

Lysosomal Storage Conditions Registry for prenatal and fetal therapies

There is one clinical trial currently open to patients with rapidly progressive infantile LALD and other lysosomal storage disorders to assess beginning enzyme replacement therapy during pregnancy before the baby is born, for patients diagnosed prenatally.

PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders) (PEARL)

ClinicalTrials.gov ID NCT04532047

Sponsor University of California, San Francisco

Information provided by Tippi Mackenzie, University of California, San Francisco (Responsible Party)

Last Update Posted 2025-03-11

Brief Summary

For detailed information, please view our study website: https://pearltrial.ucsf.edu/

The investigators aims to determine the maternal and fetal safety and feasibility of in utero fetal enzyme replacement therapy in fetuses with Lysosomal Storage Diseases.

ClinicalTrials.Gov Information

PEARL Prenatal Enzyme Replacement Therapy for Lysosomal Storage Disorders Information Link