ArticleNucleic acids research2020
Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 133 citations in OpenAlex.
- Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- Leveraging the dominant-negative effect of the kuru-protective G127V prion protein variant as a novel therapeutic strategy.Neurobiology of disease · 2026Article
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.PLoS pathogens · 2026Article
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- Chemo-omic pipeline enables discovery of prion synaptotoxic pathways and inhibitory drugs.PLoS pathogens · 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
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Leveraging the dominant-negative effect of the kuru-protective G127V prion protein variant as a novel therapeutic strategy.bioRxiv : the preprint server for biology · 2026Article
- Chemo-omic pipeline enables discovery of prion synaptotoxic pathways and inhibitory drugs.bioRxiv : the preprint server for biology · 2026Article
- Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.Acta neuropathologica communications · 2026Article
- Genome-wide screens identify core regulators of cell surface prion protein expression.Scientific reports · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
40 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
24 authors at 9 institutions in 3 countries.
Funding
Abstract
Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that <25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease.
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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.