Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease

  title={Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease},
  author={Ian Whittle and Richard S. G. Knight and Robert George Will},
  journal={Acta Neurochirurgica},
SummaryPentosan polysulphate, delivered by chronic intraventricular infusion, has been proposed as a potential therapy for human prion disease. The first treated patient is still alive several years after treatment started. Here we describe in detail a case of variant Creutzfeldt-Jakob disease in which this treatment was started at a relatively early stage but had no definite clinical benefit. The patient died from disease progression 16 months after diagnosis and 5 months after pentosan… 
Long term survival in a patient with variant Creutzfeldt–Jakob disease treated with intraventricular pentosan polysulphate
A case of a 22-year-old male with vCJD treated 19 months after the onset of clinical symptoms with continuous intraventricular PPS appeared to be safe and well tolerated and was associated with prolonged survival when compared to natural history studies, however, PPS treatment did not appear to arrest the progression of the disease.
Postmortem findings in a case of variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulfate
Treatment with iPPS did not reduce the overall neuropathological changes in the brain and the reduced peripheral immunostaining for PrP may reflect atrophy of these tissues in relation to chronic illness rather than a treatment effect.
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.
Less protease‐resistant PrP in a patient with sporadic CJD treated with intraventricular pentosan polysulphate
A patient with sporadic CJD treated with intraventricular pentosan polysulphate is treated with less protease‐resistant PrP, leading to a reduction in the chance of PrP‐resistant CJD.
Experimental treatments for human transmissible spongiform encephalopathies: is there a role for pentosan polysulfate?
Preliminary clinical experience confirms extended survival in patients with variant Creutzfeldt-Jakob disease receiving intraventricular PPS; however, it is still not clear if this is due to PPS itself, or to the accumulation of an abnormal isoform of the prion protein in the CNS.
Diphenylpyrazole-Derived Compounds Increase Survival Time of Mice after Prion Infection
A high in vitro efficiency of DPP derivatives against prion infections that was substantiated in vivo for one of these compounds is demonstrated.
Therapies for prion diseases.
Calcineurin Inhibition at the Clinical Phase of Prion Disease Reduces Neurodegeneration, Improves Behavioral Alterations and Increases Animal Survival
It is shown that the calcium-dependent phosphatase Calcineurin (CaN) is hyperactivated both in vitro and in vivo as a result of PrPSc formation, suggesting that inhibition of this phosphatases could be a target for therapy in prion diseases.
Targeting prion proteins in neurodegenerative disease
Although various promising drug candidates with antiprion activity have been identified, this proof-of-concept cannot be transferred into translational medicine yet.
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.


Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease.
Treatment Options in Patients with Prion Disease - the Role of Long Term Cerebroventricular Infusion of Pentosan Polysulphate
At present there is no proven specific or effective treatment available for any form of CJD, although some oral agents, such as quinacrine or flupirtine, are being investigated in clinical trials.
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.
Prions : food and drug safety
The role of the immune system in TSE agent neuroinvasion, Prion protein interactions and TSE infections in cell culture models, and treatment options in patients with Prion Disease are studied.
Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies.
In sporadic disease, longer survival was correlated with younger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type, and the characterization of the survival distributions, in the absence of therapy, will be an important starting point for the assessment of potential therapeutic agents in the future.
Chemoprophylaxis of scrapie in mice.
Three applications of the polyanion pentosanpolysulphate about 2 months before infection of mice with scrapie completely protected animals infected with up to 100 LD50, and considerably prolonged the
Treatment options in patients with prion disease-the role of long term cerebrovascular infusion of pentosan polysulphate. In: Kitamoto T (ed) Prions: food and drug safety
  • 2005