A New Approach to a Deadly Problem

In a major step forward for prion disease research, scientists funded by the National Institutes of Health (NIH) have developed a gene-silencing technique that significantly reduces prion protein levels in preclinical models. The study, published on 04 December 2024, offers a potential therapeutic strategy for conditions like Creutzfeldt-Jakob disease (CJD), which currently have no effective treatments.

Prion diseases are caused by misfolded proteins that trigger a cascade of neurodegeneration. These disorders are uniformly fatal and notoriously difficult to diagnose or treat. The new approach targets the PRNP gene, which encodes the prion protein, and uses RNA interference to suppress its expression.

Results from Mouse Models

In mouse models of prion disease, the gene-silencing method reduced prion protein levels by up to 80%, leading to slower disease progression and improved survival. Importantly, the prion protein is not essential for survival, making it a viable target for therapeutic suppression.

Researchers used a viral vector to deliver the silencing construct into the brain, achieving widespread distribution and sustained knockdown. No major adverse effects were observed, suggesting a favourable safety profile for future human trials.

Implications for Human Therapy

While still in early stages, this strategy could represent a paradigm shift in treating prion diseases. It also opens doors for similar approaches in other protein misfolding disorders, such as Huntington’s or certain forms of ALS.

The team is now preparing for IND-enabling studies and hopes to initiate a first-in-human trial by late 2025. If successful, this could be the first disease-modifying therapy for prion diseases, offering hope to patients and families affected by these devastating conditions.