How C9orf72 genetic changes lead to frontotemporal dementia
Official title: Defining mechanisms underlying C9orf72-associated frontotemporal dementia with C. elegans and mammalian models
Funded at Northwestern University · NIH-11263618 · Data updated 2026-11-12
Researchers use worm and mammal models to find why a C9orf72 genetic repeat causes brain cell damage in people with frontotemporal dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Northwestern University NIH-funded |
| Lab location | 1 site (Chicago, United States) |
| Project start | February 1, 2022 |
| Project end | January 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $714,576 |
| NIH project number | 5R01NS124802-05 |
| Project ID | NIH-11263618 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with a known C9orf72 repeat expansion or a family history of C9orf72-linked FTD/ALS would be most directly connected to these findings and interested in related future studies or sample donation.
✕Less likely to help
People whose dementia is caused by other genes or unrelated conditions may not directly benefit from findings specific to C9orf72 mechanisms.
What this research studies
This project models the harmful proteins made from expanded C9orf72 repeats using genetically modified C. elegans worms and mammalian systems. The team created worms that express toxic dipeptide repeat proteins (PR and GR) and ran unbiased genetic screens to find genes that block toxicity. They identified conserved genes, including the nuclear adaptor SPOP, and will test whether these same pathways protect neurons in mammalian models. The work aims to reveal biological steps that lead to neuron loss in C9orf72-linked FTD and point toward targets for future therapies.
Why it matters
Potential benefit: If successful, the research could identify molecular targets to slow or prevent neuron death in people with C9orf72-related frontotemporal dementia, guiding future treatments.
How similar studies have gone: Previous cell and animal models have shown PR and GR dipeptide repeat proteins are toxic, but linking the SPOP pathway to neurodegeneration is a novel finding that needs further validation.
Where this research is happening
-
Northwestern University
Chicago, United States Active
Researchers
- Principal investigator: Kalb, Robert G — Northwestern University
- Study coordinator: Kalb, Robert G
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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.