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In Utero Enzyme Replacement Therapy for Lysosomal Storage Diseases

a study on Mucopolysaccharidosis Mucopolysaccharidosis Type I Hunter Syndrome Mucopolysaccharidosis Type IVA Mps VII Gaucher Disease Pompe Disease Wolman Disease

Summary

Eligibility
for females ages 18-50 (full criteria)
Location
at San Francisco, California
Dates
study started
estimated completion
Principal Investigator
by Tippi MacKenzie, MD
Photo of Tippi MacKenzie
Tippi MacKenzie

Description

Summary

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

Official Title

In Utero Enzyme Replacement Therapy (ERT) for Prenatally Diagnosed Lysosomal Storage Disorders (LSDs).

Details

Because fetuses with these LSDs are at increased risk of serious perinatal morbidity and mortality, particularly in the setting of Non-Immune Hydrops Fetalis (NIHF), the administration of the approved enzyme therapy in utero has the potential to significantly improve outcomes for affected fetuses. The perinatal death rate associated with NIHF ranges from 30 to 75%, so development of an in utero approach to treatment could be of significant benefit. The in utero period has been shown to be a time of relative fetal tolerance to immune stimuli, and this tolerance may lead to improved response to ERT in situations where postnatal initiation instead leads to antibody development and impaired response to treatment. It is also probable that in some cases, initiation of ERT in utero leads to improved neurodevelopmental outcomes if the replaced enzyme impacts the neurologic system during critical periods of development. This is a phase 1 clinical trial to determine the safety and feasibility of fetal enzyme replacement therapy in fetuses with LSD

Keywords

MPS I MPS II MPS IVA MPS VI Mps VII Gaucher Disease, Type 2 Gaucher Disease, Type 3 Pompe Disease Infantile-Onset Wolman Disease Gaucher Disease Glycogen Storage Disease Type II Aldurazyme (laronidase)

Eligibility

You can join if…

Open to females ages 18-50

  • Live male or female fetuses at 18 0/7 weeks to 34 6/7 weeks gestation
  • Diagnosis of one of the 8 included LSDs in utero by genetic or enzymatic analyses performed on amniotic fluid, fetal blood, placental tissue, or other samples through chorionic villus sampling (CVS), amniocentesis, cordocentesis, cell free fetal DNA, or other procedures. In the event that parents are identified as genetic carriers for a LSD, diagnostic testing for the fetus would be performed to confirm the diagnosis
  • Pregnant women age 18 years to 50 years, carrying a live male or female fetus at 18 0/7 weeks to 34 6/7 weeks gestation
  • Identified through the above listed means to be carrying a fetus with an LSD.
  • Ability to give written informed consent and comply with the requirements of the study.

You CAN'T join if...

  • Fetuses with a concurrent severe structural anomaly
  • Fetuses with an additional pathogenic genetic variant not related to the underlying LSD that contribute a significant risk of morbidity or mortality.

Hydrops fetalis will not be an exclusion criterion because ERT has the possibility of significant benefit in this situation.

  • Women with one or more significant comorbidities that would preclude fetal intervention including, but not limited to:
  • inability to complete the procedure secondary to maternal body habitus or placental location
  • significant cardiopulmonary disease
  • mirror syndrome
  • end organ failure
  • altered mental status
  • placental abruption
  • active preterm labor
  • preterm premature rupture of membranes.
  • Mother will require therapeutic dosing of anticoagulation within 24 hours prior to or following the intervention.

Location

  • University of California
    San Francisco California 94158 United States

Lead Scientist at UCSF

  • Tippi MacKenzie, MD
    Tippi MacKenzie is a pediatric and fetal surgeon who is focused on developing better ways to diagnose and treat genetic diseases before birth. She leads a translational research lab examining the unique biology between the mother and her fetus, with the idea that pregnancy complications such as preterm labor arise from a breakdown in maternal-fetal tolerance.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT04532047
Phase
Phase 1
Study Type
Interventional
Last Updated