Experimental treatments for human transmissible spongiform encephalopathies: is there a role for pentosan polysulfate?

@article{Rainov2007ExperimentalTF,
  title={Experimental treatments for human transmissible spongiform encephalopathies: is there a role for pentosan polysulfate?},
  author={N. Rainov and Y. Tsuboi and P. Krolak-Salmon and A. Vighetto and K. Doh-Ura},
  journal={Expert Opinion on Biological Therapy},
  year={2007},
  volume={7},
  pages={713 - 726}
}
Human transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are caused by the accumulation of an abnormal isoform of the prion protein in the CNS. Creutzfeldt-Jakob disease in its sporadic form is the most frequent type of human TSE. At present, there is no proven specific or effective treatment available for any form of TSE. Pentosan polysulfate (PPS) has been shown to prolong the incubation period when administered to the cerebral ventricles in a rodent TSE model… Expand
Continuous intraventricular infusion of pentosan polysulfate: Clinical trial against prion diseases
TLDR
Although the preliminary study of the new treatment with PPS by continuous intraventricular infusion showed no apparent improvement of clinical features in patients with prion disease, the possibility of extended survival in some patients receiving long‐term PPS was suggested. Expand
Creutzfeldt‐Jakob disease: hopes for therapy
TLDR
These studies indicate that the intraventricular infusion of PPS might have some effect in prolonging survival in variant CJD, and all patients (or relatives of patients) should be given the possibility to receive a potentially useful treatment leaving clinicians with the difficulty in conducting a randomized controlled study. Expand
[New knowledge about Creutzfeldt-Jakob disease can yield therapeutic possibilities].
TLDR
Pentosan polysulphate (a drug against interstitial cystitis) infused intraventriculary in mice, prolonged the incubation time from 51 to 123 days, and the drug has been tested in patients with CJD with promising results with respect to survival time. Expand
Antibody-based immunotherapeutic attempts in experimental animal models of prion diseases
TLDR
No satisfying consequences in animals could be detected with anti-PrP antibodies directly infused into the brains of animals by the intraventricular route or by anti- PrP or anti-LRP/LR single chain fragment antibodies directly delivered into the brain by virus vector-mediated gene transfer. Expand
Protease‐resistant PrP and PrP oligomers in the brain in human prion diseases after intraventricular pentosan polysulfate infusion
  • H. Honda, K. Sasaki, +4 authors T. Iwaki
  • Medicine, Biology
  • Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2012
TLDR
Although intraventricular PPS infusion might modify the accumulation of PrP oligomers in the brains of patients with prion diseases, the therapeutic effects are still uncertain. Expand
Recent developments in therapeutics for prion diseases
TLDR
No compounds reported so far have proven to be therapeutically effective against prion diseases, due to inadequate access to brains through the blood–brain barrier, and due to lack of diagnostic indicators for presymptomatic individuals, the compounds must be given to clinically advanced patients, reducing their effectiveness. Expand
The future for treating Creutzfeldt–Jakob disease
TLDR
Novel international diagnostic criteria for including CJD patients in clinical trials in an early stage are needed and consensus should be reached for determining the most meaningful criteria to evaluate the progression of disease. Expand
[Innovation of therapeutics and prophylaxis for prion diseases].
  • K. Doh-Ura
  • Medicine
  • Rinsho shinkeigaku = Clinical neurology
  • 2009
TLDR
Preclinical diagnostic means, by which healthy prion-carriers can be revealed before the onset of the diseases, should be explored for earlier therapeutic interventions, and intrinsic disease susceptibility factors and environmental factors could solely or jointly facilitate in suppressing prion replication and disease progress. Expand
Prion Strain- and Species-Dependent Effects of Antiprion Molecules in Primary Neuronal Cultures
TLDR
It is reported that prion strains from different species can propagate in primary neuronal cultures derived from transgenic mouse lines overexpressing ovine, murine, hamster, or human prion protein. Expand
Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles.
TLDR
The acute toxicity profile of the six most promising anti-prionic compounds, the 2,4,5-trimethoxychalcones (J1, J8, J20 and J35) and the 1,3,4-oxadiazoles (Y13 and Y17) were evaluated and it was found that single oral administration of these compounds did not elicit toxicity in mice. Expand
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References

SHOWING 1-10 OF 94 REFERENCES
Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease.
TLDR
Pentosan polysulphate (PPS), a large polyglycoside molecule with weak heparin-like activity, has been shown to prolong the incubation period of the intracerebral infection when administered to the cerebral ventricles in a rodent scrapie model. Expand
Prophylactic potential of pentosan polysulphate in transmissible spongiform encephalopathies
TLDR
Although direct testing of the efficacy of PS in reducing susceptibility to variant CJD is not possible, further animal studies are essential to examine the possible use of PS for risk reduction, as PS is only effective if given close to scrapie injection. Expand
Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent
TLDR
It is shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species, providing strong evidence that the same agent strain is involved in both BSE and vCJD. Expand
Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models
TLDR
It is indicated that intraventricular PPS infusion might be useful for the treatment of transmissible spongiform encephalopathies in humans, providing that the therapeutic dosage is carefully evaluated. Expand
The epidemics of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: current status and future prospects.
TLDR
Better control measures are necessary to guard against the possibility of iatrogenic transmission through blood transfusion or contaminated surgical instruments, and these measures will required sensitive and specific, diagnostic tests and improved decontamination methods. Expand
Effectiveness of Polyene Antibiotics in Treatment of Transmissible Spongiform Encephalopathy in Transgenic Mice Expressing Syrian Hamster PrP Only in Neurons
TLDR
The effectiveness of treatment after intracerebral scrapie infection in transgenic mice expressing PrP only in neurons suggested that neurons are important sites of action for these drugs. Expand
Pathology of variant Creutzfeldt-Jakob disease.
  • J. Ironside
  • Medicine
  • Archives of virology. Supplementum
  • 2000
TLDR
The neuropathology of vCJD is characterised by the florid plaque, composed of a central amyloid core with a fibrillary periphery, surrounded by a rim of spongiform change in an intact neuropil. Expand
A systematic review of prion therapeutics in experimental models.
TLDR
A comprehensive systematic, rather than selective, review of published data on experimental approaches to prion therapeutics is presented to provide a scientific resource for informing future therapeutics research, both in laboratory models and in clinical studies. Expand
Evaluation of Quinacrine Treatment for Prion Diseases
TLDR
Despite its ability to cross the blood-brain barrier, the use of quinacrine for the treatment of CJD is questionable, at least as a monotherapy, and the multistep experimental approach employed here could be used to test new therapeutic regimes before their use in human trials. Expand
The molecular biology of prion propagation.
TLDR
The conformational change known to be central to prion propagation, from a predominantly alpha-helical fold to one predominantly comprising beta structure, can now be reproduced in vitro, and the ability of beta-PrP to form fibrillar aggregates provides a plausible molecular mechanism for prions propagation. Expand
...
1
2
3
4
5
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