How a C9orf72 repeat makes toxic proteins in ALS and frontotemporal dementia
Official title: Hexanucleotide repeat translation in ALS and Frontotemporal Dementia
Funded at University of Michigan at Ann Arbor · NIH-11333790 · Data updated 2026-11-12
Researchers are figuring out how a repeated DNA segment in the C9orf72 gene leads cells to make harmful repeat proteins that can contribute to ALS and frontotemporal dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Michigan at Ann Arbor NIH-funded |
| Lab location | 1 site (Ann Arbor, United States) |
| Project start | September 1, 2016 |
| Project end | March 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $640,460 |
| NIH project number | 5R01NS099280-09 |
| Project ID | NIH-11333790 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with ALS or FTD who carry the C9orf72 hexanucleotide repeat, or family members known to have the repeat, would be the most relevant candidates for donating samples or joining related clinical efforts.
✕Less likely to help
Patients without the C9orf72 repeat or those seeking immediate clinical treatment are unlikely to receive direct benefit from this basic research.
What this research studies
This project aims to identify which RNA molecules inside cells serve as templates for the repeat-associated non-AUG (RAN) translation that creates dipeptide repeat proteins. The team will test whether repeat-containing lariat RNAs or newly started linear RNAs with a 5' cap produce these toxic proteins using cellular and molecular experiments. They will also study how the RNA's structure and the cell's ribosome quality control systems affect translation start sites and ribosome stalling during protein production. Experiments will use laboratory models and human-derived material as available, conducted at the University of Michigan.
Why it matters
Potential benefit: If successful, the work could reveal molecular targets to stop production of toxic repeat proteins and guide new therapies or biomarkers for C9orf72-related ALS/FTD.
How similar studies have gone: Prior laboratory studies have shown that manipulating RAN translation or ribosomal quality control can reduce toxic effects in cell and animal models, but translation to human treatments has not yet been achieved.
Where this research is happening
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University of Michigan at Ann Arbor
Ann Arbor, United States Active
Researchers
- Principal investigator: Todd, Peter K — University of Michigan at Ann Arbor
- Study coordinator: Todd, Peter K
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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.