How mixed dipeptide repeat proteins form and harm nerve cells in C9orf72 ALS/FTD
Mechanisms of chimeric DPR production and toxicity in c9ALS/FTD
This work aims to find how mixed dipeptide repeat proteins form and damage brain and nerve cells in people with C9orf72-related ALS and frontotemporal dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Emory University NIH-funded |
| Lab location | 1 site (Atlanta, United States) |
| Project ID | NIH-11327394 on NIH RePORTER |
What this research studies
If you have C9orf72-linked ALS or FTD, this project focuses on why abnormal repeat sequences in the C9orf72 gene produce several dipeptide repeat proteins (DPRs) and why some of those proteins clump and harm neurons. The team will study two non-standard ways cells make DPRs—repeat-associated non-AUG (RAN) translation and initiation at a near-cognate CUG codon—and will look for 'chimeric' DPRs that combine features of different DPR types. They will use lab-grown neurons, 3-D cell models, and comparisons with a related repeat disorder (SCA36) to see why some DPRs stay soluble while others form toxic inclusions. The goal is to identify specific steps in DPR production or aggregation that could be targeted to prevent nerve-cell damage.
Who could benefit from this research
Good fit: People diagnosed with ALS or FTD who carry the C9orf72 hexanucleotide repeat expansion or who can donate tissue or blood for research are most relevant to this work.
Not a fit: People without the C9orf72 repeat expansion or those with non-C9 forms of ALS/FTD are less likely to directly benefit from findings focused on C9-specific DPR mechanisms.
Why it matters
Potential benefit: If successful, this work could reveal molecular steps that researchers can target to stop DPR aggregation or toxicity and slow neurodegeneration in C9orf72 ALS/FTD.
How similar studies have performed: Prior work has shown DPRs are made in C9orf72 disorders and in SCA36, but the generation of chimeric DPRs and the exact reasons some DPRs aggregate are still largely novel and underexplored.
Where this research is happening
Atlanta, United States
- Emory University — Atlanta, United States (Active)
Researchers
- Principal investigator: Mceachin, Zachary Thomas — Emory University
- Study coordinator: Mceachin, Zachary Thomas
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.