Evidence map›Paper›PMID 31558565›Full record

ArticleMolecular & cellular proteomics : MCP2019

Domain-specific Quantification of Prion Protein in Cerebrospinal Fluid by Targeted Mass Spectrometry.

Eric Vallabh Minikel, Eric Kuhn, Alexandra R Cocco, Sonia M Vallabh, Christina R Hartigan, Andrew G Reidenbach, Jiri G Safar, Gregory J Raymond, Michael D McCarthy, Rhonda O'Keefe and 6 more

Open access · hybridAbstract readValidation Study
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  6. Biomarker changes preceding symptom onset in genetic prion disease.medRxiv : the preprint server for health sciences · 2023
    Article
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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

16 authors at 6 institutions in 4 countries.

Eric Vallabh MinikelChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115; Prion Alliance, Cambridge, MA 02139; Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142. Electronic address: minikel@broadinstitute.org.
Eric KuhnProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115.
Alexandra R CoccoProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Sonia M VallabhChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115; Prion Alliance, Cambridge, MA 02139.
Christina R HartiganProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Andrew G ReidenbachChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Jiri G SafarDepartments of Pathology and Neurology Case Western Reserve University, Cleveland, OH 44106.
Gregory J RaymondLaboratory of Persistent Viral Diseases, NIAID Rocky Mountain Labs, Hamilton, MT 59840.
Michael D McCarthyEnvironmental Health and Safety, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Rhonda O'KeefeEnvironmental Health and Safety, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Franc LlorensNational Reference Center for TSE, Georg-August University, Göttingen, 37073, Germany; Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), L'Hospitalet de Llobregat, 08908, Barcelona, Spain.
Inga ZerrNational Reference Center for TSE, Georg-August University, Göttingen, 37073, Germany.
Sabina CapellariIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, 40139, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 40123, Italy.
Piero ParchiIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, 40139, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, 40138, Italy.
Stuart L SchreiberChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142; Department of Chemistry & Chemical Biology, Harvard University, Cambridge, MA 02138.
Steven A CarrProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142. Electronic address: scarr@broad.mit.edu.
Broad Institute · USIstituti di Ricovero e Cura a Carattere Scientifico · ITBiomedical Research Networking Center on Neurodegenerative Diseases · ESCase Western Reserve University · USHarvard University · USUniversity of Göttingen · DE

Funding

MICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0M
Center of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4M
Replication mechanism of human prionsR01NS103848 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI SAFAR, JIRI G., SUREWICZ, WITOLD K · 2018 to 2022
$2.6M
Biomarkers to enable ASO prevention trials in genetic prion disease carriersR21TR003040 · NCATS · MASSACHUSETTS GENERAL HOSPITAL · PI ARNOLD, STEVEN E · 2019 to 2020
$485k
Developing in vitro assays to identify small molecules that inhibit human prionsF31AI122592 · NIAID · HARVARD MEDICAL SCHOOL · PI MINIKEL, ERIC VALLABH · 2016 to 2018
$99k
NCATS NIH HHS R21 TR003040NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210986NIAID NIH HHS F31 AI122592NINDS NIH HHS R01 NS103848
6 · The paper itself

Abstract

Therapies currently in preclinical development for prion disease seek to lower prion protein (PrP) expression in the brain. Trials of such therapies are likely to rely on quantification of PrP in cerebrospinal fluid (CSF) as a pharmacodynamic biomarker and possibly as a trial endpoint. Studies using PrP ELISA kits have shown that CSF PrP is lowered in the symptomatic phase of disease, a potential confounder for reading out the effect of PrP-lowering drugs in symptomatic patients. Because misfolding or proteolytic cleavage could potentially render PrP invisible to ELISA even if its concentration were constant or increasing in disease, we sought to establish an orthogonal method for CSF PrP quantification. We developed a multi-species targeted mass spectrometry method based on multiple reaction monitoring (MRM) of nine PrP tryptic peptides quantified relative to an isotopically labeled recombinant protein standard for human samples, or isotopically labeled synthetic peptides for nonhuman species. Analytical validation experiments showed process replicate coefficients of variation below 15%, good dilution linearity and recovery, and suitable performance for both CSF and brain homogenate and across humans as well as preclinical species of interest. In

Indexed as

AnimalsDrug DevelopmentEnzyme-Linked Immunosorbent AssayHumansMacaca fascicularisMass SpectrometryMicePrion DiseasesPrion ProteinsRatsPrion Proteinsbiomarker: diagnosticcerebrospinal fluidCreutzfeldt-Jakob diseasemultiple reaction monitoringneurodegenerative diseasesprionTargeted mass spectrometry

Identifiers

PMID31558565
PMCPMC6885701
OpenAlexW2975210295

What OpenQuestion holds

Textmetadata
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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.