Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease

@article{Whittle2006UnsuccessfulIP,
  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},
  year={2006},
  volume={148},
  pages={677-679}
}
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… 
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Long term survival in a patient with variant Creutzfeldt–Jakob disease treated with intraventricular pentosan polysulphate
TLDR
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
TLDR
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
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.
Less protease‐resistant PrP in a patient with sporadic CJD treated with intraventricular pentosan polysulphate
TLDR
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?
TLDR
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
TLDR
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.
TLDR
The clinicians might face several specific problems when evaluating the efficacy of the drug in CJD, such as rareness of the disease, lack of appropriate preclinical tests and heterogeneous clinical presentation in humans, which have to be carefully addressed in future.
Calcineurin Inhibition at the Clinical Phase of Prion Disease Reduces Neurodegeneration, Improves Behavioral Alterations and Increases Animal Survival
TLDR
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
TLDR
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
TLDR
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.
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