Anle138b prevents PrP plaque accumulation in Tg(PrP-A116V) mice but does not mitigate clinical disease.

Anle138b is an anti-aggregating compound previously shown to delay the onset of scrapie, a transmissible prion disease, although its in vivo efficacy against other prion disease subtypes has not been fully assessed. TgGSS mice that model Gerstmann-Sträussler-Scheinker disease (GSS) via expression of mouse PrP accumulate PrP amyloid plaques in their brains and develop progressive ataxia leading to death in ~160 days. When allowed to feed on food pellets containing anle138b from weaning until death, the brains of TgGSS mice displayed significant reductions in PrP plaque burden, insoluble PrP, and proteinase K-resistant PrP at end stage, compared with TgGSS mice allowed to feed on placebo food pellets.