Evidence map›Paper›PMID 39605733›Full record

ArticlebioRxiv : the preprint server for biology2024

PrP turnover in vivo and the time to effect of prion disease therapeutics.

Taylor L Corridon, Jill O'Moore, Yuan Lian, Vanessa Laversenne, Briana Noble, Nikita G Kamath, Fiona E Serack, Abdul Basit Shaikh, Brian Erickson, Craig Braun and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Taylor L CorridonProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0009-0002-4167-8291
Jill O'MooreWeissman Hood Institute, Great Falls, MT, 59405, USA.
Yuan LianProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0009-0001-9565-2292
Vanessa LaversenneProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Briana NobleIonis Pharmaceuticals, Carlsbad, CA, 92010, USA.
Nikita G KamathProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Fiona E SerackProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Abdul Basit ShaikhCharles River Laboratories, Worcester, MA, 01605, USA.
Brian EricksonIQ Proteomics, Framingham, MA, 01702, USA.
Craig BraunIQ Proteomics, Framingham, MA, 01702, USA.
Kenney LenzComparative Medicine, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Michael HowardComparative Medicine, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Nathan ChanComparative Medicine, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Andrew G ReidenbachProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Deborah E CabinWeissman Hood Institute, Great Falls, MT, 59405, USA.
Sonia M VallabhProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0000-0003-3824-2702
Andrea GrindelandWeissman Hood Institute, Great Falls, MT, 59405, USA.
Nina OberbeckGate Bio, Brisbane, CA, 94005, USA.
Hien T ZhaoIonis Pharmaceuticals, Carlsbad, CA, 92010, USA.
Eric Vallabh MinikelProgram in Brain Health, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0000-0003-2206-1608

Funding

Modulation of Exosome Release for Functional Restoration in Age-related Retinal DisordersP20GM152335 · NIGMS · MC LAUGHLIN RESEARCH INSTITUTE · PI Brenda F Canine · 2024 to 2026
$11.1M
Biomarkers and Mechanisms of PrP Misfolding, Mutation, and DeficiencyR01NS132022 · NINDS · BROAD INSTITUTE, INC. · PI Eric Vallabh Minikel · 2024 to 2026
$1.9M
NIGMS NIH HHS P20 GM152335NINDS NIH HHS R01 NS132022
6 · The paper itself

Abstract

PrP lowering is effective against prion disease in animal models and is being tested clinically. Therapies in the current pipeline lower PrP production, leaving pre-existing PrP to be cleared according to its own half-life. We hypothesized that PrP's half-life may be a rate-limiting factor for the time to effect of PrP-lowering drugs, and one reason why late treatment of prion-infected mice is not as effective as early treatment. Using isotopically labeled chow with targeted mass spectrometry, as well as antisense oligonucleotide treatment followed by timed PrP measurement, we estimate a half-life of 5-6 days for PrP in the brain. PrP turnover is not affected by over- or under-expression. Mouse PrP and human PrP have similar turnover rates measured in wild-type or humanized knock-in mice. CSF PrP appears to mirror brain PrP in real time in rats. PrP is more readily quantifiable in colon than in other peripheral organs, and appears to have a shorter half-life in colon than in brain. Our data may inform the design of both preclinical and clinical studies of PrP-lowering drugs.

Identifiers

PMID39605733
PMCPMC11601496

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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.