Document Type
Article
Publication Title
Nucleic Acids Research
Publisher
Oxford University Press
Publication Date
8-2020
Volume
48
Issue
19
Disciplines
Medical Sciences | Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
Abstract
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)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that
DOI
10.1093/nar/gkaa616
Rights
Copyright - The Author(s) 2020
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Minikel, Eric Vallabh; Zhao, Hien T.; Le, Jason; O'Moore, Jill; Pitstick, Rose; Graffam, Samantha; Carlson, George A.; and Kavanaugh, Michael P., "Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints" (2020). Biomedical and Pharmaceutical Sciences Faculty Publications. 71.
https://scholarworks.umt.edu/biopharm_pubs/71