Evidence map›Paper›PMID 29637732›Full record

ArticleCPT: pharmacometrics & systems pharmacology2018

Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1.

Joshua F Apgar, Jian-Ping Tang, Pratap Singh, Nanda Balasubramanian, John Burke, Michael R Hodges, Melissa A Lasaro, Lin Lin, Bjorn L Millard, Kristi Moore and 4 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
6.2field-weighted citation impact, top 4% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 44 citations in OpenAlex.

  1. New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  2. Article
  3. Review
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  5. Review
  6. Review
  7. Article
  8. Modeling onActa pharmaceutica Sinica. B · 2024
    Article
  9. Review
  10. Article
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  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice.Frontiers in bioengineering and biotechnology · 2022
    Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Joshua F ApgarApplied BioMath, Lincoln, Massachusetts, USA.
Jian-Ping TangAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Pratap SinghAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Nanda BalasubramanianAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
John BurkeApplied BioMath, Lincoln, Massachusetts, USA.
Michael R HodgesAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Melissa A LasaroAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Lin LinApplied BioMath, Lincoln, Massachusetts, USA.
Bjorn L MillardApplied BioMath, Lincoln, Massachusetts, USA.
Kristi MooreAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Lucy S JunAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Susan SobolovAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Anna Katharina WilkinsApplied BioMath, Lincoln, Massachusetts, USA.
Xiang GaoAlexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.
Alexion Pharmaceuticals (United States) · USApplied BioMath (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Crigler-Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by a marked decrease in uridine-diphosphate-glucuronosyltransferase (UGT1A1) enzyme activity. Delivery of hUGT1A1-modRNA (a modified messenger RNA encoding for UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients. To support translation from preclinical to clinical studies, and first-in-human studies, a quantitative systems pharmacology (QSP) model was developed. The QSP model was calibrated to plasma and liver mRNA, and total serum bilirubin in Gunn rats, an animal model of CN1. This QSP model adequately captured the observed plasma and liver biomarker behavior across a range of doses and dose regimens in Gunn rats. First-in-human dose projections made using the translated model indicated that 0.5 mg/kg Q4W dose should provide a clinically meaningful and sustained reduction of >5 mg/dL in total bilirubin levels.

Indexed as

AnimalsBilirubinCrigler-Najjar SyndromeDisease Models, AnimalGenetic TherapyGlucuronosyltransferaseHumansLiverModels, TheoreticalNanoparticlesRatsRats, GunnRNARNA, MessengerTreatment OutcomeUGT1A1 EnzymeBilirubinGlucuronosyltransferaseRNARNA, MessengerUGT1A1 Enzyme

Identifiers

PMID29637732
PMCPMC6391595
OpenAlexW2797686837

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.