Evidence map›Paper›PMID 37955580›Full record

ReviewPrenatal diagnosis2023

Intrauterine enzyme replacement therapies for lysosomal storage disorders: Current developments and promising future prospects.

Akos Herzeg, Beltran Borges, Billie R Lianoglou, Juan Gonzalez-Velez, Emma Canepa, Dane Munar, Sarah P Young, Deeksha Bali, Michel H Gelb, Pranesh Chakraborty and 4 more

Registry-linked trialOpen access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Prenatal diagnosis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04532047 (PEARL), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04532047 phase1recruitingnot on this map

PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)

TypeinterventionalSponsorUniversity of California, San FranciscoRan2021 to 2032Enrolled10ConditionsMPS I, MPS II, MPS IVA, MPS VIArmsAldurazyme (laronidase)
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Current Status of Cellular and Gene-Based Therapies for Congenital Metabolic Disorders: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  9. Article
  10. Review
  11. Prenatal Delivery of Enzyme Replacement Therapy to Fetuses Affected by Early-Onset Lysosomal Storage Diseases.American journal of medical genetics. Part C, Seminars in medical genetics · 2025
    Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Akos HerzegCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.ORCID 0000-0002-2061-4099
Beltran BorgesCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.
Billie R LianoglouCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.
Juan Gonzalez-VelezCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.
Emma CanepaCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.
Dane MunarCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.
Sarah P YoungDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Deeksha BaliDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Michel H GelbDepartment of Chemistry, University of Washington, Seattle, Washington, USA.
Pranesh ChakrabortyDepartment of Pediatrics, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada.
Priya S KishnaniDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Paul HarmatzBenioff Children's Hospital, University of California, San Francisco, California, USA.
Jennifer L CohenDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Tippi C MacKenzieCenter for Maternal-Fetal Precision Medicine, University of California, San Francisco, California, USA.
University of California, San Francisco · USDuke University · USUniversity of Ottawa · CAUniversity of Washington · US

Funding

Phase 1 Study of In Utero Enzyme Replacement Therapy for the Treatment of Lysosomal Storage DiseasesR01HD110270 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Tippi Mackenzie · 2022 to 2026
$3.3M
NICHD NIH HHS R01 HD110270
6 · The paper itself

Abstract

Lysosomal storage disorders (LSDs) are a group of monogenic condition, with many characterized by an enzyme deficiency leading to the accumulation of an undegraded substrate within the lysosomes. For those LSDs, postnatal enzyme replacement therapy (ERT) represents the standard of care, but this treatment has limitations when administered only postnatally because, at that point, prenatal disease sequelae may be irreversible. Furthermore, most forms of ERT, specifically those administered systemically, are currently unable to access certain tissues, such as the central nervous system (CNS), and furthermore, may initiate an immune response. In utero enzyme replacement therapy (IUERT) is a novel approach to address these challenges evaluated in a first-in-human clinical trial for IUERT in LSDs (NCT04532047). IUERT has numerous advantages: in-utero intervention may prevent early pathology; the CNS can be accessed before the blood-brain barrier forms; and the unique fetal immune system enables exposure to new proteins with the potential to prevent an immune response and may induce sustained tolerance. However, there are challenges and limitations for any fetal procedure that involves two patients. This article reviews the current state of IUERT for LSDs, including its advantages, limitations, and potential future directions for definitive therapies.

Indexed as

Enzyme Replacement TherapyLysosomal Storage DiseasesCentral Nervous SystemFemaleHumansLysosomesPregnancy

Identifiers

PMID37955580
PMCPMC11155627
OpenAlexW4388630440

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.