Frequently Asked Questions

You may be able to join the study if you are:

• Pregnant, and
• Age 18 or over, and
• Your fetus has been diagnosed with or is at risk for one of the diseases.

You may not be able to join if you or your fetus have other conditions that impact your safety.

If you are interested in learning more about Prenatal ERT, contact us. You do not have to meet eligibility criteria before contacting the study team. We are happy to speak with you about the study at any time. Our team can work with your local provider to facilitate genetic testing to confirm the diagnosis if needed.

A clinical trial is a type of research project that involves treatment and people. In the PEARL Trial, we are testing to see if enzyme replacement therapy (ERT) given before birth is safe for the mother and fetus. We also want to see if the health outcomes for children who start ERT before birth are better than the outcomes for children who start ERT after birth. Clinical trials help researchers answer questions like:

• Is the new treatment safe?
• Does the new treatment do what it is supposed to do?
• Is the new treatment better than a current treatment?
• Which patients benefit the most from the new treatment?

Lysosomal storage diseases (LSDs) are enzyme deficiencies that can lead to disabling or fatal damage to organs, including muscles, bones, heart, brain, liver, spleen, and others. The human body makes and uses hundreds of proteins called enzymes. Enzymes help our cells and bodies work well. Enzymes break down fats, sugars, and other materials into simpler forms that can be used or discarded by the body. Without enzymes, fat, sugars, and other materials will build up in cells. They can reach harmful levels that damage vital organs. Lysosomal storage diseases (LSD) are rare, inherited diseases. People with LSDs have a genetic difference (mutation) that stops the creation of a well-functioning enzyme. While each LSD is a rare disease, together they affect 1 in 5,000 births worldwide.

For some LSDs, including those in the PEARL Trial, there is an FDA-approved enzyme replacement therapy (ERT) available. ERT is a medication that replaces the enzyme that is normally produced by the human body. Babies, children, and adults with these conditions may receive ERT through intravenous (IV) infusion every 1-2 weeks for life.

The PEARL Trial is the first clinical trial to use ERT to treat lysosomal storage diseases before birth. Waiting until birth to start ERT has drawbacks.

• Adverse reactions to the medication can complicate long-term treatment.
• ERT, when given after birth, cannot cross the blood-brain barrier to get to the brain, where it is needed.
• Postnatal ERT will not reverse the damage that starts during fetal development.

UCSF's FDA-approved PEARL clinical trial aims to address these drawbacks by treating fetuses before birth. The goal is to improve outcomes and survival rates compared to treatments that start after birth.

A maternal-fetal medicine specialist will place a needle through the mother's belly to reach the umbilical cord. The provider uses an ultrasound machine to guide the injection into the umbilical cord. The fetus will receive ERT every 2-4 weeks during pregnancy. This procedure is very safe. It is the same procedure that doctors have used for intrauterine blood transfusions for over 40 years.
 

The mother receives numbing medicine in the belly and will not feel the ERT injection. General anesthesia (where the patient is put to sleep with medicine) is not needed for the procedure. Other medications may be given to ensure the mother is comfortable.

To join the study, you and a support person need to travel to UCSF in San Francisco, California, every 2-4 weeks for ERT. Another option is to move to San Francisco temporarily. Financial support is available for both options. You may deliver your baby at your local hospital or, if you have relocated, at UCSF. After birth, the baby will receive standard care for their LSD. This includes getting ongoing ERT with your local medical provider. Our team will follow the health of your child for 5 years after birth. You will need to return to UCSF with your child once a year for follow-up visits. There is financial support for travel or relocation for prenatal ERT infusions and annual UCSF visits.

The study team will talk with you in detail about all risks before you decide to come to UCSF. While unlikely to occur, possible risks for both the mother and fetus include infection, miscarriage, and premature delivery.

The goals of giving ERT before birth are to:

• Prevent organ damage
• Improve the health of the baby at birth
• Prevent antibody creation against the ERT long-term. Antibodies are proteins the body makes to protect it from germs or other substances and can limit how well ERT works.

The study team will talk to you about the potential costs and financial support before you travel to UCSF. The PEARL Trial pays for:

• Research-related expenses
• Travel expenses for Prenatal ERT infusions
• Travel to UCSF for one-year follow-up visit

"PEARL" comes from "PrEnAtal enzyme Replacement for Lysosomal storage diseases." The trial is also called "In Utero Enzyme Replacement Therapy for Fetuses with Lysosomal Storage Diseases."