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

Katsumi Doh-Ura, Kensuke Ishikawa, Ikuko Murakami-Kubo, Kensuke Sasaki, Shirou Mohri, Richard Race, Toru Iwaki

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4999-5006
Number of pages8
JournalJournal of virology
Volume78
Issue number10
DOIs
Publication statusPublished - May 1 2004

Fingerprint

Pentosan Sulfuric Polyester
Intraventricular Infusions
pentosans
Prion Diseases
prion diseases
Animal Models
animal models
drugs
Pharmaceutical Preparations
therapeutics
mice
Therapeutics
dosage
PrPSc Proteins
quinacrine
PrPSc proteins
brain
Quinacrine
hematoma
protein deposition

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models. / Doh-Ura, Katsumi; Ishikawa, Kensuke; Murakami-Kubo, Ikuko; Sasaki, Kensuke; Mohri, Shirou; Race, Richard; Iwaki, Toru.

In: Journal of virology, Vol. 78, No. 10, 01.05.2004, p. 4999-5006.

Research output: Contribution to journalArticle

Doh-Ura, Katsumi ; Ishikawa, Kensuke ; Murakami-Kubo, Ikuko ; Sasaki, Kensuke ; Mohri, Shirou ; Race, Richard ; Iwaki, Toru. / Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models. In: Journal of virology. 2004 ; Vol. 78, No. 10. pp. 4999-5006.
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