What controls abnormal repeat-driven protein production in brain diseases
Defining modifiers and mechanisms of RAN translation
['FUNDING_R01'] · STANFORD UNIVERSITY · NIH-11318923
Researchers are looking at how unusual protein-making from repeated DNA sequences creates toxic proteins in Alzheimer’s, frontotemporal dementia, and ALS to find ways to stop that damage.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | STANFORD UNIVERSITY (nih funded) |
| Locations | 1 site (STANFORD, UNITED STATES) |
| Trial ID | NIH-11318923 on ClinicalTrials.gov |
What this research studies
From a patient perspective, the team is studying a weird way cells sometimes make proteins from repeated DNA pieces that can produce harmful peptides in neurodegenerative diseases. They combine single-molecule biophysics, genetic experiments, biochemical tests, and animal models to see how this process (called RAN translation) happens and which factors change it. The labs also follow up on a new finding about altered processing at the ends of some messenger RNAs that are linked to FTD and ALS. Findings from cells and animals will be used to spot molecular 'modifiers' that reduce toxic protein production and test whether those changes lessen degeneration in model systems.
Who could benefit from this research
Good fit: People with Alzheimer’s disease, frontotemporal dementia, or ALS—especially those known or suspected to have nucleotide repeat expansions—would be the most relevant patient group for this work.
Not a fit: Patients with cognitive symptoms due to non-neurodegenerative causes (for example, pure vascular dementia or reversible metabolic problems) are unlikely to directly benefit from these findings.
Why it matters
Potential benefit: If successful, this work could reveal targets to reduce toxic repeat-made proteins and slow or prevent neuron loss in several dementias and ALS.
How similar studies have performed: Previous laboratory studies have identified modifiers that reduced degeneration in cell and animal models, but applying these discoveries to people is still early and unproven.
Where this research is happening
STANFORD, UNITED STATES
- STANFORD UNIVERSITY — STANFORD, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: PUGLISI, JOSEPH D — STANFORD UNIVERSITY
- Study coordinator: PUGLISI, JOSEPH D
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions: Alzheimer disease dementia, Alzheimer syndrome, Alzheimer's Disease