Chemoprophylaxis of scrapie in mice

Diringer, Heino; Ehlers, Bernhard

doi:10.1099/0022-1317-72-2-457

Cited by 118 publications

(62 citation statements)

References 27 publications

(23 reference statements)

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“…Effectiveness was clearly observed even for the infusion at a late stage of infection, when abnormal PrP deposition was already visible in the affected brain. PPS is known to be effective in inhibiting abnormal PrP formation in vitro (5) and/or in prolonging the disease incubation time in vivo (9,12,13,16). However, its effectiveness in vivo has been restricted to administration either before or soon after peripheral infection.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models

Doh‐ura

Ishikawa

Murakami-Kubo

et al. 2004

J Virol

207

173

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The therapeutic efficacy of direct drug infusion into the brain, the target organ of transmissible spongiform encephalopathies, was assessed in transgenic mice intracerebrally infected with 263K scrapie agent. Pentosan polysulfate (PPS) gave the most dramatic prolongation of the incubation period, and amphotericin B had intermediate effects, but antimalarial drugs such as quinacrine gave no significant prolongation. Treatment with the highest dose of PPS at an early or late stage of the infection prolonged the incubation time by 2.4 or 1.7 times that of the control mice, respectively. PPS infusion decreased not only abnormal prion protein deposition but also neurodegenerative changes and infectivity. These alterations were observed within the brain hemisphere fitted with an intraventricular infusion cannula but not within the contralateral hemisphere, even at the terminal disease stage long after the infusion had ended. Therapeutic effects of PPS were also demonstrated in mice infected with either RML agent or Fukuoka-1 agent. However, at doses higher than that providing the maximal effects, intraventricular PPS infusion caused adverse effects such as hematoma formation in the experimental animals. These findings indicate that intraventricular PPS infusion might be useful for the treatment of transmissible spongiform encephalopathies in humans, providing that the therapeutic dosage is carefully evaluated.

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models

Doh‐ura

Ishikawa

Murakami-Kubo

et al. 2004

J Virol

207

173

View full text Add to dashboard Cite

show abstract

“…Thus, IgG Abs could enhance agent uptake into myeloid cells, which may in turn heighten agent replication (22,31). Chemoprophylaxis studies on scrapie similarly implicate a crucial role for myeloid cells in spreading peripheral infection (32).…”

Section: Discussionmentioning

confidence: 99%

Neuroinvasion by a Creutzfeldt–Jakob disease agent in the absence of B cells and follicular dendritic cells

Shlomchik

Radebold

Duclos

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…One class of molecules that has shown significant efficiency in the treatment of prion diseases is the class of sulfated polyanions, such as dextran sulfate 500 (DS500), pentosane polysulfate and suramin (Farquhar & Dickinson, 1986;Kimberlin & Walker, 1986;Ladogana et al, 1992;Caughey & Raymond, 1993;Beringue et al, 2000;Gilch et al, 2001). However, their use is limited by their toxicity, restricted efficiency and narrow window of intervention following infection (Diringer & Ehlers, 1991;Ladogana et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

A novel generation of heparan sulfate mimetics for the treatment of prion diseases

Adjou

Simoneau

Salès

et al. 2003

Journal of General Virology

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Chemoprophylaxis of scrapie in mice

Cited by 118 publications

References 27 publications

Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models

Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models

Neuroinvasion by a Creutzfeldt–Jakob disease agent in the absence of B cells and follicular dendritic cells

A novel generation of heparan sulfate mimetics for the treatment of prion diseases

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