Evidence map›Paper›PMID 37517328›Full record

ArticleMolecular genetics and metabolism2023

Elevated cerebrospinal fluid ubiquitin C-terminal hydrolase-L1 levels correlate with phenotypic severity and therapeutic response in Niemann-Pick disease, type C1.

Niamh X Cawley, Spencer Giddens, Nicole M Farhat, Rachel A Luke, Katelin E J Scott, Hibaaq O Mohamed, An Dang Do, Elizabeth Berry-Kravis, Stephanie M Cologna, Fang Liu and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Alterations in Proteostasis Mechanisms in Niemann-Pick Type C Disease.International journal of molecular sciences · 2024
    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

11 authors at 3 institutions in 1 country.

Niamh X CawleySection on Molecular Dysmorphology, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Spencer GiddensApplied and Computational Mathematics and Statistics, University of Notre Dame, South Bend, IN, USA.
Nicole M FarhatSection on Molecular Dysmorphology, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Rachel A LukeSection on Molecular Dysmorphology, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Katelin E J ScottSection on Molecular Dysmorphology, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Hibaaq O MohamedSection on Molecular Dysmorphology, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
An Dang DoUnit on Cellular Stress in Development and Diseases, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Elizabeth Berry-KravisRush University Medical Center, Chicago, IL, USA.
Stephanie M ColognaDepartment of Chemistry and Laboratory of Integrative Neuroscience, University of Illinois Chicago, Chicago, IL, USA.
Fang LiuApplied and Computational Mathematics and Statistics, University of Notre Dame, South Bend, IN, USA.
Forbes D PorterSection on Molecular Dysmorphology, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: fdporter@mail.nih.gov.
University of Notre Dame · USRush University Medical Center · USUniversity of Illinois Chicago · US

Funding

Basic and Translational Studies of Inborn Errors of MetabolismZIAHD008988 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PORTER, FORBES · 2020 to 2025
$12.7M
Clinical Investigations of Inborn Errors of MetabolismZIAHD008989 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PORTER, FORBES · 2020 to 2025
$5.1M
Research Investigations of Cellular Stress in Development and DiseasesZIAHD009001 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DANG DO, AN · 2022 to 2025
$4.9M
Intramural NIH HHS ZIA HD008988Intramural NIH HHS ZIA HD008989
6 · The paper itself

Abstract

backgroundNiemann-Pick disease, type C1 (NPC1) is an ultrarare, recessive disorder due to pathological variants of NPC1. The NPC1 phenotype is characterized by progressive cerebellar ataxia and cognitive impairment. Although classically a childhood/adolescent disease, NPC1 is heterogeneous with respect to the age of onset of neurological signs and symptoms. While miglustat has shown to be clinically effective, there are currently no FDA approved drugs to treat NPC1. Identification and characterization of biomarkers may provide tools to facilitate therapeutic trials. Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a protein which is highly expressed by neurons and is a biomarker of neuronal damage. We thus measured cerebrospinal fluid (CSF) levels of UCHL1 in individuals with NPC1.

methodsCSF levels of UCHL1 were measured using a Quanterix Neuroplex 4 assay in 94 individuals with NPC1 and 35 age-appropriate comparison samples. Cross-sectional and longitudinal CSF UCHL1 levels were then evaluated for correlation with phenotypic measures and treatment status.

resultsCSF UCHL1 levels were markedly elevated (3.3-fold) in individuals with NPC1 relative to comparison samples. The CSF UCHL1 levels showed statistically significant (adj p < 0.0001), moderate, positive correlations with both the 17- and 5-domain NPC Neurological Severity Scores and the Annual Severity Increment Scores. Miglustat treatment significantly decreased (adj p < 0.0001) CSF UCHL1 levels by 30% (95% CI 17-40%).

conclusionsCSF UCHL1 levels are elevated in NPC1, increase with increasing clinical severity and decrease in response to therapy with miglustat. Based on these data, UCHL1 may be a useful biomarker to monitor disease progression and therapeutic response in individuals with NPC1.

Indexed as

Niemann-Pick Disease, Type C1-DeoxynojirimycinAdolescentBiomarkersChildCross-Sectional StudiesHumansPhenotypeUbiquitin Thiolesterase1-DeoxynojirimycinBiomarkersmiglustatUbiquitin ThiolesteraseUCHL1 protein, humanBiomarkerMiglustatNiemann-Pick disease, type C1NPC1Ubiquitin C-terminal hydrolase-L1UCHL1

Identifiers

PMID37517328
PMCPMC10803635
OpenAlexW4385155191

What OpenQuestion holds

Textmetadata
LicenceTDM
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.