Correcting abnormal RNA splicing in ALS and frontotemporal dementia
Targeting Dysregulated RNA Splicing in Neurodegenerative Diseases
Researchers are using patient-derived lab-grown nerve and brain cells to develop ways to fix abnormal RNA splicing that harms people with ALS or frontotemporal dementia.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Massachusetts General Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11177725 on NIH RePORTER |
What this research studies
This project grows human stem-cell-derived versions of six disease-relevant brain and nerve cell types from people with ALS/FTD and uses long-read RNA sequencing to map abnormal splicing patterns. The team will study RNA-binding proteins such as TDP-43 and FUS to understand why they move to the wrong place in cells and cause harmful mis-splicing. Researchers will test molecular approaches in these patient-derived cells to try to restore normal splicing and gene expression. The goal is to identify specific targets and strategies that could lead to therapies to protect nerve cells.
Who could benefit from this research
Good fit: Ideal candidates are people diagnosed with ALS or frontotemporal dementia who can consent to donate blood or skin samples for generation of patient-derived cells or who may join future related clinical efforts.
Not a fit: People without an ALS or FTD diagnosis or those unable or unwilling to provide tissue samples are unlikely to directly benefit from participating in this lab-focused project.
Why it matters
Potential benefit: If successful, this work could reveal molecular targets and approaches to restore normal RNA splicing, creating new paths toward treatments that slow or prevent nerve cell loss in ALS and FTD.
How similar studies have performed: Prior work has linked TDP-43–related mis-splicing to ALS/FTD and corrected individual mis-splicing events in cells, but applying long-read sequencing across many cell types and reversing widespread mis-splicing is a newer and more experimental approach.
Where this research is happening
Boston, United States
- Massachusetts General Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Lagier-Tourenne, Clotilde — Massachusetts General Hospital
- Study coordinator: Lagier-Tourenne, Clotilde
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.