Evidence map›Paper›PMID 23966247›Full record

ArticleNeurology2013

HTRF analysis of soluble huntingtin in PHAROS PBMCs.

Miriam Moscovitch-Lopatin, Rachel E Goodman, Shirley Eberly, James J Ritch, H Diana Rosas, Samantha Matson, Wayne Matson, David Oakes, Anne B Young, Ira Shoulson and 2 more

Open access · bronzeAbstract readMulticenter Study
In one paragraph

Article in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Peripheral Biomarkers in Manifest and Premanifest Huntington's Disease.International journal of molecular sciences · 2023
    Review
  4. Review
  5. Article
  6. Article
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

12 authors at 2 institutions in 1 country.

Miriam Moscovitch-LopatinFrom the Massachusetts General Hospital (M.M.-L., R.E.G., J.J.R., H.D.R., S.M., A.B.Y., S.M.H.), MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Charlestown, MA; University of Rochester Medical Center (S.E., D.O.), Department of Biostatistics and Computational Biology, Rochester, NY; Veterans Administration Hospital (W.M.), Bedford, MA; and Program for Regulatory Science & Medicine (I.S.), Georgetown University, Washington, DC.
Rachel E Goodman
Shirley Eberly
James J Ritch
H Diana Rosas
Samantha Matson
Wayne Matson
David Oakes
Anne B Young
Ira Shoulson
Steven M Hersch
Huntington Study Group PHAROS Investigators
United States Department of Veterans Affairs · USUniversity of Rochester Medical Center · US

Funding

Prospective Huntington At Risk Observational Study (PHAROS)R01HG002449 · NHGRI · UNIVERSITY OF ROCHESTER · PI SHOULSON, IRA · 2002 to 2009
$7.6M
Neuroimaging Biomarkers for disease-modyfying therapies in Hintington's diseaseP01NS058793 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HERSCH, STEVEN M · 2008 to 2012
$6.6M
Blood Level of Huntingtin: A Biomarker for Huntington's DiseaseU01NS071789 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HERSCH, STEVEN M · 2010 to 2014
$3.4M
NHGRI NIH HHS HG02449-01NHGRI NIH HHS R01 HG002449NINDS NIH HHS P01 NS058793NINDS NIH HHS P01NS058793NINDS NIH HHS U01 NS071789NINDS NIH HHS UO1NS071789
6 · The paper itself

Abstract

objectiveWe measured the levels of mutant huntingtin (mtHtt) and total huntingtin (tHtt) in blood leukocytes from Prospective Huntington At-Risk Observational Study (PHAROS) subjects at 50% risk of carrying the Huntington disease mutation using a homogeneous time-resolved fluorescence (HTRF) assay to assess its potential as a biomarker.

methodsPeripheral blood mononuclear cells from consenting PHAROS subjects were analyzed by HTRF using antibodies that simultaneously measured mtHtt and tHtt. mtHtt levels were normalized to tHtt, double-stranded DNA, or protein and analyzed according to cytosine-adenine-guanine repeat length (CAGn), demographics, predicted time to clinical onset or known time since clinical onset, and available clinical measures.

resultsFrom 363 assayed samples, 342 met quality control standards. Levels of mtHtt and mt/tHtt were higher in 114 subjects with expanded CAG repeats (CAG ≥ 37) compared with 228 subjects with nonexpanded CAG repeats (CAG <37) (p < 0.0001). Analysis of relationships to predicted time to onset or to phenoconversion suggested that the HTRF signal could mark changes during the Huntington disease prodrome or after clinical onset.

conclusionsThe HTRF assay can effectively measure mtHtt in multicenter sample sets and may be useful in trials of therapies targeting huntingtin.

Indexed as

ObservationAdultClinical Trials as TopicDouble-Blind MethodFemaleFluorescence Resonance Energy TransferFrontal LobeHumansHuntingtin ProteinHuntington DiseaseLeukocytes, MononuclearLongitudinal StudiesMaleMiddle AgedMutationNerve Tissue ProteinsHTT protein, humanHuntingtin ProteinNerve Tissue Proteins

Identifiers

PMID23966247
PMCPMC3795598
OpenAlexW2100566384

What OpenQuestion holds

Textmetadata
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.