Waking up the healthy MECP2 gene to treat Rett syndrome with an XIST-targeting ASO
Advancing an XIST ASO candidate for the treatment of Rett Syndrome
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 ID | NIH-11322750 on NIH RePORTER |
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.
Who could benefit from this research
Good fit: Girls with genetically confirmed Rett syndrome caused by MECP2 mutations would be the intended candidates for this approach.
Not a fit: People whose symptoms are not caused by MECP2 mutations, those with MECP2 duplications, or individuals with two nonfunctional MECP2 copies are unlikely to benefit.
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 performed: 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
Boston, United States
- Massachusetts General Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Lee, Jeannie T — Massachusetts General Hospital
- Study coordinator: Lee, Jeannie T
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.