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

  title={Experimental treatments for human transmissible spongiform encephalopathies: is there a role for pentosan polysulfate?},
  author={Nikolai G. Rainov and Yasushi Tsuboi and Pierre Krolak-Salmon and A. Vighetto and Katsumi Doh-ura},
  journal={Expert Opinion on Biological Therapy},
  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… 
Continuous intraventricular infusion of pentosan polysulfate: Clinical trial against prion diseases
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.
Creutzfeldt‐Jakob disease: hopes for therapy
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.
Antibody-based immunotherapeutic attempts in experimental animal models of prion diseases
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.
Protease‐resistant PrP and PrP oligomers in the brain in human prion diseases after intraventricular pentosan polysulfate infusion
  • H. Honda, K. Sasaki, T. Iwaki
  • Medicine, Biology
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2012
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.
The future for treating Creutzfeldt–Jakob disease
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.
Prion Strain- and Species-Dependent Effects of Antiprion Molecules in Primary Neuronal Cultures
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.
Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles.
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.
Systematic review of therapeutic interventions in human prion disease
Based on published information identified by this review, survival of most treated patients is within the ranges reported in the untreated patient series, and disease course and treatment of all patients must be evaluated within a structured framework, preferably within randomized controlled trials.
Insights from Therapeutic Studies for PrP Prion Disease.
Recent advances in prion-related therapeutic research are reviewed and basic scientific issues to be resolved for meaningful medical intervention of prion disease are discussed.
Rapidly progressive dementias and the treatment of human prion diseases
This article begins with an overview of the etiologies and diagnostic work-up of RPD followed by a detailed review of the literature concerning the treatment of human prion diseases (1971 to present).


Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease.
Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent
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.
Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models
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.
Effectiveness of Polyene Antibiotics in Treatment of Transmissible Spongiform Encephalopathy in Transgenic Mice Expressing Syrian Hamster PrP Only in Neurons
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.
Pathology of variant Creutzfeldt-Jakob disease.
  • J. Ironside
  • Biology
    Archives of virology. Supplementum
  • 2000
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.
A systematic review of prion therapeutics in experimental models.
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.
Evaluation of Quinacrine Treatment for Prion Diseases
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.
The molecular biology of prion propagation.
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.
Quinacrine does not prolong survival in a murine Creutzfeldt‐Jakob disease model
This work studied the utility of quinacrine in a well‐characterized in vivo model of mouse‐adapted transmissible spongiform encephalopathy and failed to show any evidence that qu inacrine is effective when using the simple but objective measure of survival prolongation.