Although the practice of molecular medicine has taken enormous strides in recent years—as attested to by a wave of approvals of antisense oligonucleotide (ASO) therapies as well as the first CRISPR-based therapy—neurodegenerative diseases, such as prion disease, Huntington’s disease, Alzheimer’s disease, and Parkinson’s disease, remain a difficult challenge. Toxic protein aggregation has been implicated in neurodegeneration, pointing to gene silencing as a broadly applicable therapeutic strategy. Although ASOs and CRISPR-based silencing offer potential to suppress the expression of pathogenic proteins, efforts have not yet been successful. On page 1421 of this issue, Neumann et al. (1) report a new epigenetic editor that can silence the expression of prion protein (PrP) in the brains of mice and offers a fresh approach to the treatment of neurodegenerative diseases.

https://www.science.org/doi/10.1126/science.ado7082

https://www.science.org/doi/10.1126/science.adq3334