ArticlePLoS pathogens2009
Continuous quinacrine treatment results in the formation of drug-resistant prions.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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
88 citing papers in PubMed, 153 citations in OpenAlex.
- Trial
- Article
- Prion Diseases-When Proteins Turn Lethal: Creutzfeldt-Jakob Disease (CJD) and the Quest for Classification, Diagnosis, Therapeutic Approaches, and Emerging Research.Molecules (Basel, Switzerland) · 2026Review
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Therapeutic strategies in prion disease: current evidence, translational challenges, and emerging directions.Frontiers in neuroscience · 2026Review
- Oligosaccharyltransferase (OST) complex inhibition effectively treats rodent and human prions.PLoS pathogens · 2026Article
- Classical BSE emergence from Nor98/atypical scrapie: Unraveling the shift vs. selection dichotomy in the prion field.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A review on current theories and potential therapies for prion diseases.Molecular biology reports · 2025Review
- Reactive Microglia and Astrocytes as Therapeutic Targets in Prion Diseases.Sub-cellular biochemistry · 2025Review
- Article
- Screening of Anti-Prion Compounds Using the Protein Misfolding Cyclic Amplification Technology.Biomolecules · 2024Article
- Creutzfeldt-Jakob disease and other prion diseases.Nature reviews. Disease primers · 2024Review
- New implications for prion diseases therapy and prophylaxis.Frontiers in molecular neuroscience · 2024Review
- Multiple aspects of amyloid dynamicsFrontiers in molecular neuroscience · 2024Article
- A tetracationic porphyrin with dual anti-prion activity.iScience · 2023Article
- Prion therapeutics: Lessons from the past.Prion · 2022Review
- Alternating anti-prion regimens reduce combination drug resistance but do not further extend survival in scrapie-infected mice.The Journal of general virology · 2021Article
- Environmental and host factors that contribute to prion strain evolution.Acta neuropathologica · 2021Review
- Unfolded and intermediate states of PrP play a key role in the mechanism of action of an antiprion chaperone.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
28 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
7 authors at 2 institutions in 1 country.
Funding
Abstract
Quinacrine is a potent antiprion compound in cell culture models of prion disease but has failed to show efficacy in animal bioassays and human clinical trials. Previous studies demonstrated that quinacrine inefficiently penetrates the blood-brain barrier (BBB), which could contribute to its lack of efficacy in vivo. As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR(0/0) mice that are deficient in mdr1a and mdr1b genes. Mice treated with 40 mg/kg/day of quinacrine accumulated up to 100 microM of quinacrine in their brains without acute toxicity. PrP(Sc) levels in the brains of prion-inoculated MDR(0/0) mice diminished upon the initiation of quinacrine treatment. However, this reduction was transient and PrP(Sc) levels recovered despite the continuous administration of quinacrine. Treatment with quinacrine did not prolong the survival times of prion-inoculated, wild-type or MDR(0/0) mice compared to untreated mice. A similar phenomenon was observed in cultured differentiated prion-infected neuroblastoma cells: PrP(Sc) levels initially decreased after quinacrine treatment then rapidly recovered after 3 d of continuous treatment. Biochemical characterization of PrP(Sc) that persisted in the brains of quinacrine-treated mice had a lower conformational stability and different immunoaffinities compared to that found in the brains of untreated controls. These physical properties were not maintained upon passage in MDR(0/0) mice. From these data, we propose that quinacrine eliminates a specific subset of PrP(Sc) conformers, resulting in the survival of drug-resistant prion conformations. Transient accumulation of this drug-resistant prion population provides a possible explanation for the lack of in vivo efficacy of quinacrine and other antiprion drugs.
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.