Waking up the healthy MECP2 gene to treat Rett syndrome with an XIST-targeting ASO
Official title: Advancing an XIST ASO candidate for the treatment of Rett Syndrome
Funded at Massachusetts General Hospital · NIH-11322750 · Data updated 2026-11-12
A treatment that aims to wake up the healthy MECP2 gene on the silent X chromosome to help girls with Rett syndrome.
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 | July 1, 2019 |
| Project end | February 28, 2029 |
| Funding year | 2026 |
| Award (this year) | $787,051 |
| NIH project number | 5R01MH118351-08 |
| Project ID | NIH-11322750 on NIH RePORTER |
Who could benefit from this research
✓Could help
Girls with genetically confirmed Rett syndrome caused by MECP2 mutations would be the intended candidates for this approach.
✕Less likely to help
People whose symptoms are not caused by MECP2 mutations, those with MECP2 duplications, or individuals with two nonfunctional MECP2 copies are unlikely to benefit.
What this research studies
Researchers are developing an antisense oligonucleotide (ASO) that targets XIST RNA to reactivate the healthy MECP2 gene on the inactivated X chromosome. They plan to pair the ASO with a small drug that reduces DNA methylation to make reactivation more effective. In mice, this approach has restored MECP2 protein in the brain and improved Rett-like symptoms, and the team is now advancing a candidate toward the safety and development steps needed for people. The work is led at Massachusetts General Hospital with the goal of creating a therapy for girls with MECP2-related Rett syndrome.
Why it matters
Potential benefit: If successful, this approach could restore MECP2 function in the brain and improve or reverse neurological symptoms of Rett syndrome.
How similar studies have gone: Previous mouse studies have shown that restoring MECP2 expression can reverse symptoms, and the XIST-ASO strategy builds on those promising preclinical results though it is novel for human use.
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
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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.