How metformin, PKR, and head injury affect C9orf72-linked ALS/FTD
Molecular effects of metformin, PKR and TBI on C9orf72 ALS/FTD
This project looks at whether metformin and lowering PKR activity reduce toxic repeat-related proteins and how prior head injury may change those effects for adults with C9orf72-linked ALS/FTD.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Florida NIH-funded |
| Lab location | 1 site (Gainesville, United States) |
| Project ID | NIH-10795768 on NIH RePORTER |
What this research studies
Researchers are studying how the G4C2 repeat expansion in C9orf72 leads to toxic repeat-associated (RAN) proteins that may drive ALS and FTD. They examine how the integrated stress response and the enzyme PKR increase RAN protein production and whether metformin or PKR inhibitors can lower those proteins. Work combines laboratory experiments and C9orf72 mouse models with analysis of human tissue samples and links with traumatic brain injury. The team will test whether blocking PKR or giving metformin improves neuron health and behavior in models and whether similar signatures appear in human autopsies.
Who could benefit from this research
Good fit: Adults with C9orf72-linked ALS or FTD, people with a family history of the C9orf72 expansion, or patients willing to donate tissue or clinical information (including those with prior head injury) would be the most relevant participants.
Not a fit: People whose ALS/FTD is caused by unrelated mechanisms without C9orf72 expansions or RAN protein accumulation are less likely to benefit directly from these approaches.
Why it matters
Potential benefit: If successful, this work could point to treatments—including repurposing metformin or PKR-targeting drugs—that lower toxic proteins and may slow or prevent C9orf72-related ALS/FTD.
How similar studies have performed: Preclinical work in C9orf72 mouse models showed that metformin and PKR inhibition lowered RAN proteins and improved outcomes, but these strategies have not yet been proven effective in people.
Where this research is happening
Gainesville, United States
- University of Florida — Gainesville, United States (Active)
Researchers
- Principal investigator: Ranum, Laura P.w — University of Florida
- Study coordinator: Ranum, Laura P.w
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.