ArticleJCI insight2022
Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- PrP turnover in vivo and the time to effect of prion disease therapeutics.PLoS pathogens · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide screens identify core regulators of cell surface prion protein expression.Scientific reports · 2026Article
- Prion protein (PrP) profiles in blood and CSF: insights into pre-symptomatic and symptomatic prion disease.Brain communications · 2026Article
- In vivo base editing extends lifespan of a humanized mouse model of prion disease.Nature medicine · 2025Article
- Cellular Prion Protein and Amyloid-β Oligomers in Alzheimer's Disease-Are There Connections?International journal of molecular sciences · 2025Review
- The dynamics of prion spreading is governed by the interplay between the non-linearities of tissue response and replication kinetics.iScience · 2024Article
- The prion protein is required for normal responses to light stimuli by photoreceptors and bipolar cells.iScience · 2024Article
- Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion.Neurology · 2024Article
- Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor.Science (New York, N.Y.) · 2024Article
- Modulation of prion protein expression through cryptic splice site manipulation.bioRxiv : the preprint server for biology · 2023Article
- Biomarker changes preceding symptom onset in genetic prion disease.medRxiv : the preprint server for health sciences · 2023Article
- A single-cell map of antisense oligonucleotide activity in the brain.Nucleic acids research · 2023Article
- Therapeutic Trial of anle138b in Mouse Models of Genetic Prion Disease.Journal of virology · 2023Article
- A single-cell map of antisense oligonucleotide activity in the brain.bioRxiv : the preprint server for biology · 2023Article
- Analysis of non-human primate models for evaluating prion disease therapeutic efficacy.PLoS pathogens · 2022Article
- Prion protein gene mutation detection using long-read Nanopore sequencing.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically and pharmacologically validated therapeutic target for prion disease. In order to evaluate PrP concentration as a pharmacodynamic biomarker and assess its contribution to known prion disease risk factors, we developed and validated a plate-based immunoassay reactive for PrP across 6 species of interest and applicable to brain and cerebrospinal fluid (CSF). PrP concentration varied dramatically across different brain regions in mice, cynomolgus macaques, and humans. PrP expression did not appear to contribute to the known risk factors of age, sex, or common PRNP genetic variants. CSF PrP was lowered in the presence of rare pathogenic PRNP variants, with heterozygous carriers of P102L displaying 55%, and D178N just 31%, of the CSF PrP concentration of mutation-negative controls. In rodents, pharmacologic reduction of brain Prnp RNA was reflected in brain parenchyma PrP and, in turn in CSF PrP, validating CSF as a sampling compartment for the effect of PrP-lowering therapy. Our findings support the use of CSF PrP as a pharmacodynamic biomarker for PrP-lowering drugs and suggest that relative reduction from individual baseline CSF PrP concentration may be an appropriate marker for target engagement.
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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.