How DNA chemical marks near the C9orf72 gene affect ALS and FTD
Epigenetic Mechanisms Contributing to the Pathogenesis of ALS/FTD with GGGGCC Repeat Expansion Mutation at the C9orf72 Locus
['FUNDING_R01'] · COLUMBIA UNIVERSITY HEALTH SCIENCES · NIH-11375222
This project will use CRISPR-based tools to add or remove DNA methylation near the C9orf72 repeat to try to alter disease processes in people who carry the C9orf72 mutation.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | COLUMBIA UNIVERSITY HEALTH SCIENCES (nih funded) |
| Locations | 1 site (NEW YORK, UNITED STATES) |
| Trial ID | NIH-11375222 on ClinicalTrials.gov |
What this research studies
If you carry the C9orf72 repeat mutation, researchers will look at chemical marks on your DNA called methylation that can change how the gene behaves. The team will use a CRISPR/dCas9-based methylation editor to add or remove methyl groups at the repeat region and nearby CpG islands in patient-derived cells and laboratory models. They will measure the effects on harmful RNA foci, toxic dipeptide repeat proteins, and C9orf72 gene expression to see whether changing methylation reduces disease signals. The work aims to identify whether targeting methylation could modify when symptoms start or how fast they progress.
Who could benefit from this research
Good fit: Ideal candidates are people who carry the G4C2 hexanucleotide repeat expansion in C9orf72 or have a family history of C9orf72-related ALS/FTD and who can provide cells or biological samples for research.
Not a fit: People whose ALS/FTD is caused by other genes or non-genetic forms of the disease are unlikely to benefit directly from this C9orf72-focused work.
Why it matters
Potential benefit: If successful, this research could point to new treatments that modify DNA methylation to reduce toxic products and slow or prevent ALS/FTD in C9orf72 mutation carriers.
How similar studies have performed: Prior studies show that higher methylation at the C9orf72 repeat correlates with altered gene expression and may affect disease, but using CRISPR-based methylation editing is a newer approach with promising early results in lab models and not yet proven in patients.
Where this research is happening
NEW YORK, UNITED STATES
- COLUMBIA UNIVERSITY HEALTH SCIENCES — NEW YORK, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: LIU, X. SHAWN — COLUMBIA UNIVERSITY HEALTH SCIENCES
- Study coordinator: LIU, X. SHAWN
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: Amyotrophic Lateral Sclerosis Motor Neuron Disease