Correcting abnormal RNA splicing in ALS and frontotemporal dementia
Official title: Targeting Dysregulated RNA Splicing in Neurodegenerative Diseases
Funded at Massachusetts General Hospital · NIH-11177725 · Data updated 2026-11-12
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 start | September 1, 2023 |
| Project end | August 31, 2028 |
| Funding year | 2025 |
| Award (this year) | $1,621,934 |
| NIH project number | 5RM1NS133601-03 |
| Project ID | NIH-11177725 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
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.
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.
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 gone: 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
-
Massachusetts General Hospital
Boston, United States Active
Researchers
- Principal investigator: Lagier-Tourenne, Clotilde — Massachusetts General Hospital
- Study coordinator: Lagier-Tourenne, Clotilde
Related research
Other NIH-funded projects on the same topics.
-
Developing small molecules to treat TDP-43 related brain diseases
A potential new drug candidate (XL20) for diseases like Alzheimer’s and other dementias linked to TDP-43 protein problems is being developed and refined for people who live with these conditions.
-
Tau filament structure in Alzheimer’s and related dementias
Aims to map the detailed 3D shapes of tau protein filaments found in human brain diseases to help develop better diagnostics and treatments for Alzheimer’s-related dementias.
-
Targeting RNA Splicing Abnormalities in ALS/FTD
A research team aims to understand and correct abnormal RNA splicing in ALS and related brain diseases to help patients in the future.
-
Blood-brain barrier–friendly imaging agents for neurodegenerative diseases
A researcher team will test new imaging agents that can cross the brain barrier to help detect Alzheimer’s and related diseases earlier and more accurately.
-
Brain cell–derived EV markers to differentiate Alzheimer’s and related dementias
A Mayo Clinic team is testing brain-cell–specific tiny particles in blood to tell apart Alzheimer’s disease and similar dementias using advanced machine-learning analysis.
-
Fisetin approach to reduce vulnerability to community infections in aging veterans
A patient-friendly look at a study testing whether the natural compound fisetin can help aging Veterans stay healthier when they face common infections.
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.