ArticleJCI insight2019
Antisense oligonucleotides extend survival of prion-infected mice.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Understanding Creutzfeldt-Jakob disease in Iran: a systematic review of case reports.The Journal of international medical research · 2024Pooled it
- Life at the interface: Byron Caughey's search for prion disease inhibitors through chemistry, structure, and cell physiology.Acta neuropathologica · 2026Review
- Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 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
- The octapeptide repeats of prion protein play critical roles in the pathogenesis of prion diseases.Acta neuropathologica communications · 2026Article
- A model-based prion vaccine protects a transgenic mouse line carrying a Gerstmann-Sträussler-Scheinker disease mutation.Acta neuropathologica · 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
- Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Review
- Review
- Genome-wide screens identify core regulators of cell surface prion protein expression.Scientific reports · 2026Article
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Recent advancements in QuIC-based diagnostic assays for sporadic and inherited prion diseases: focusing on the emerging role of ES-QuIC.Frontiers in neuroscience · 2026Review
- Therapeutic strategies in prion disease: current evidence, translational challenges, and emerging directions.Frontiers in neuroscience · 2026Review
- Prion protein (PrP) profiles in blood and CSF: insights into pre-symptomatic and symptomatic prion disease.Brain communications · 2026Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Prion disease is a fatal, incurable neurodegenerative disease of humans and other mammals caused by conversion of cellular prion protein (PrP; PrPC) into a self-propagating neurotoxic conformer (prions; PrPSc). Strong genetic proofs of concept support lowering PrP expression as a therapeutic strategy. Antisense oligonucleotides (ASOs) can provide a practical route to lowering one target mRNA in the brain, but their development for prion disease has been hindered by three unresolved questions from prior work: uncertainty about mechanism of action, unclear potential for efficacy against established prion infection, and poor tolerability of drug delivery by osmotic pumps. Here we test antisense oligonucleotides (ASOs) delivered by bolus intracerebroventricular injection to intracerebrally prion-infected wild-type mice. Prophylactic treatments given every 2-3 months extended survival times 61-98%, and a single injection at 120 days post-infection, near the onset of clinical signs, extended survival 55% (87 days). In contrast, a non-targeting control ASO was ineffective. Thus, PrP lowering is the mechanism of action of ASOs effective against prion disease in vivo, and infrequent, or even single, bolus injections of ASOs can slow prion neuropathogenesis and markedly extend survival, even when initiated near clinical signs. These findings should empower development of PrP-lowering therapy for prion disease.
Indexed as
Identifiers
What OpenQuestion holds
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.