A wide range of observations indicate that a reduction in the levels of the cellular prion protein (PrPC) is both safe and can extend survival of prion diseases. The promise that this treatment avenue offers has recently been validated in rodent studies, which evaluated antisense oligonucleotides or virus-delivered gene therapy vectors that ablate PrPC production. The clinical translation of these treatments to humans still faces formidable challenges in their safe delivery and the projected high costs of their broad dissemination.

This work will investigate a small molecule that has been optimized for reaching the brain after oral administration and reduces PrPC levels when assessed on a wide range of human cells. The treatment compound belongs to a clinically well understood compound class of cardiac glycosides that are inexpensive to produce. The main specific goal of this study is to establish if the oral administration of our lead compound can extend survival of prion diseases by lowering PrPC brain levels in an animal model. The study will also investigate if a PrPC lowering capacity of the compound in the brain can be monitored by drawing blood samples and measuring the PrPC levels in white blood cells at suitable intervals throughout the study.