How levels of the normal prion protein change how fast prion disease moves

How Substrate Dosage Drives Prion Disease Kinetics

NIH-funded research Broad Institute, INC. · NIH-11238466

This project looks at whether lowering the normal prion protein can slow or change the speed of prion disease for people affected by prion disorders.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionBroad Institute, INC. NIH-funded
Lab location1 site (Cambridge, United States)
Project IDNIH-11238466 on NIH RePORTER

What this research studies

Researchers will use animal models (including mice) and patient-derived prion samples to see how different amounts of the normal prion protein (PrP) change the steps of prion disease, such as initial misfolding, replication, and nerve damage. They will test genetic models with lower or higher PrP and use prion-lowering drugs called antisense oligonucleotides (ASOs) to mimic potential treatments. The team will compare effects across different prion strains and species and include spontaneous (not experimentally inoculated) disease models. Findings aim to show how PrP dosage relates to survival and which parts of the disease process are most affected by lowering PrP.

Who could benefit from this research

Good fit: Ideal candidates for sample donation or future trials would be people diagnosed with sporadic, familial, or acquired prion disease or individuals willing to provide biological samples for research.

Not a fit: People without prion disease or those expecting an immediate treatment benefit should not expect direct personal benefit from this basic and preclinical research at this stage.

Why it matters

Potential benefit: If successful, this work could guide PrP-lowering therapies that slow disease progression or extend survival for people with prion disease.

How similar studies have performed: Prior animal studies and early preclinical work with PrP-lowering antisense oligonucleotides have shown promise, and this project builds on those findings while addressing new questions about timing, species, and strain differences.

Where this research is happening

Cambridge, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.