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.