R-loop target to reactivate FMR1 in Fragile X syndrome
Official title: R-loop-induced CGG contraction as a therapeutic approach for Fragile X syndrome
Funded at Massachusetts General Hospital · NIH-11295216 · Data updated 2026-11-12
A patient-friendly approach aims to reactivate the FMR1 gene in people with Fragile X syndrome using a novel genetic strategy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Massachusetts General Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | June 1, 2026 |
| Project end | March 31, 2031 |
| Funding year | 2026 |
| Award (this year) | $824,998 |
| NIH project number | 1R01MH137056-01A1 |
| Project ID | NIH-11295216 on NIH RePORTER |
Who could benefit from this research
✓Could help
Individuals with Fragile X syndrome who carry the FMR1 gene silencing and relevant autism/anxiety features.
✕Less likely to help
Patients without Fragile X–related FMR1 silencing or those not fitting the study’s genetic criteria may not benefit.
What this research studies
This project explores a genetic approach to restore FMR1 activity, which could potentially reduce core symptoms of Fragile X syndrome. Researchers are examining how R-loops and CGG repeat contractions might unlock the silenced gene in affected individuals. The work involves advanced 3-D modeling, specialized AAV-based delivery, and brain-cell studies to understand how reactivating FMR1 affects neurons and circuits linked to autism and anxiety. If successful, the findings could inform future therapies that modify the disease process rather than just symptoms.
Why it matters
Potential benefit: If successful, the approach could pave the way for disease-modifying treatments that improve cognitive and behavioral outcomes.
How similar studies have gone: Previous efforts show that restoring FMR1 expression can improve FXS phenotypes in models, with translational potential awaiting validation in humans.
Where this research is happening
-
Massachusetts General Hospital
Boston, United States Active
Researchers
- Principal investigator: Lee, Jeannie T — Massachusetts General Hospital
- Study coordinator: Lee, Jeannie T
Related research
Other NIH-funded projects on the same topics.
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Understanding Fragile X Syndrome: How it progresses and affects daily life
A long-term study using existing Fragile X data to map how the condition changes over time in children and young adults, including how autism, race, and location influence outcomes.
-
Sleep and mood links in Fragile X Syndrome
A short, patient-friendly study to understand how sleep problems relate to mood and depressive symptoms in people with Fragile X–linked autism.
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Connecting 3D genome misfolding to gene silencing in Fragile X syndrome
A study in people with Fragile X syndrome focuses on how 3D genome folding errors may turn off important genes, contributing to the condition’s features.
-
Cortical circuit problems in Fragile X mice and people
Researchers are studying how brain circuits go awry in Fragile X syndrome by comparing mice and people to understand why certain brain rhythms and responses are altered.
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Brain biology in fragile X syndrome: how brain signals unfold and vary in patients
This grant supports research to understand brain signals and why symptoms vary in people with fragile X syndrome, aiming to translate findings into better care.
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Brain research on Fragile X Syndrome to improve therapies
A multi-year program studies brain function and differences in Fragile X Syndrome to help develop better treatments for people with FXS.
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.