Doh-ura K et al. 2004. Treatment of TSE by intraventricular drug infusion in animal models (J Virol 78:4999-5006)

This is a preclinical paper from Kyushu University in Fukuoka with a co-author at the NIAID Rocky Mountain Laboratories, published in the Journal of Virology in May 2004. It asked whether a drug placed directly in the brain could treat a transmissible spongiform encephalopathy (TSE) in transgenic mice infected with the 263K scrapie agent. Pentosan polysulfate (PPS) delayed disease most, amphotericin B did so moderately, and quinacrine-type antimalarials did not significantly lengthen the incubation period. The effect was local to the infused hemisphere, and higher doses were harmful. The authors suggested that intraventricular PPS might be useful for human TSE if the dose is set carefully. The paper is the animal basis cited for the later human PPS infusions; see approach-intraventricular-pentosan-polysulfate. Aggregate findings only; information only, not medical advice.

Key facts

  • The citation is verified: seven authors, Journal of Virology 2004, volume 78, issue 10, pages 4999-5006, doi 10.1128/jvi.78.10.4999-5006.2004, PMID 15113880, PMCID PMC400350.
  • The first six listed authors worked at Kyushu University, Fukuoka (Neuropathology, plus Mohri at the Center of Biomedical Research); Richard Race is listed at the Laboratory of Persistent Viral Diseases, NIAID Rocky Mountain Laboratories.
  • The model was transgenic mice infected in the brain with the 263K scrapie agent, with drugs delivered into the brain rather than under the skin.
  • PPS gave the biggest delay: at the highest dose tested the incubation period reached 2.4 times control when treatment began early and 1.7 times when it began late.
  • Amphotericin B had a moderate effect, while quinacrine and related antimalarials did not significantly extend the incubation period.
  • PPS lowered abnormal prion protein, neurodegeneration and infectivity, but only in the hemisphere carrying the infusion cannula, and the effect was still visible at terminal disease long after infusion ended.
  • PPS also helped in mice infected with the RML or Fukuoka-1 agents, so the effect was not limited to 263K.
  • Doses above the most effective level caused harm, including hematoma formation, which is why the authors tied any human use to careful dose finding.
  • By the Crossref count the paper had been cited 198 times, and Europe PMC indexes 161 citing records.

Timeline

  1. 2004Europe PMC record created for the paper, ahead of the May issue.
  2. 2004Journal of Virology prints the paper in volume 78, issue 10 (publisher date in Crossref).
  3. 2022Takatsuki and colleagues publish on PPS and low-level persistent prion infection, one of many later papers citing this work (title only seen).
  4. 2023Shijo and colleagues publish on protein properties in a genetic CJD form in response to pentosan, also citing this paper (title only seen).

Last checked 1 November 2026

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