Rapidly progressive dementias (RPDs) are a group of heterogeneous disorders that include
immune-mediated, infectious and metabolic encephalopathies, as well as prion diseases …

Prion diseases share common clinical and pathological characteristics such as spongiform
neuronal degeneration and deposition of an abnormal form of a host-derived protein, termed …

Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly
throughout the central nervous system (CNS). By modulating RNA, they hold the promise of …

Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-
propagating conformations, leading to rapid-onset dementia and death. However …

Naturally occurring human genetic variants that are predicted to inactivate protein-coding
genes provide an in vivo model of human gene inactivation that complements knockout …

The genetic basis for most inherited neurodegenerative diseases has been identified, yet
there are limited disease-modifying therapies for these patients. A new class of drugs …

Human prion diseases are remarkable for long incubation times followed typically by rapid
clinical decline. Seed amplification assays and neurodegeneration biofluid biomarkers are …

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic
hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO) …

Protein aggregation is a hallmark of neurodegenerative diseases. However, the mechanism
that induces pathogenic aggregation is not well understood. Recently, it has emerged that …

Attaining sufficient tissue exposure at the site of action to achieve the desired
pharmacodynamic effect on a target is an important determinant for any drug discovery …