Finding the genes behind X-linked dystonia-parkinsonism
Official title: Assembling the Genetic Architecture of X-linked Dystonia Parkinsonism
Funded at Massachusetts General Hospital · NIH-11285328 · Data updated 2026-11-12
This project looks for specific genetic changes linked to X-linked dystonia-parkinsonism and explores laboratory approaches to correct those changes for people affected by the condition.
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 | September 1, 2017 |
| Project end | December 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $662,257 |
| NIH project number | 5R01NS102423-08 |
| Project ID | NIH-11285328 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are people with genetically confirmed X-linked dystonia-parkinsonism (TAF1 SVA-associated mutations) or family members willing to provide samples for genetic and cellular studies.
✕Less likely to help
People whose movement disorder is caused by other genes or who lack the TAF1 SVA mutation, or those with very advanced disease, may not receive direct benefit from this research.
What this research studies
From a patient perspective, the team is comparing genomes and RNA from affected people to pinpoint the DNA change that disrupts the TAF1 gene and harms striatal neurons. They use patient-derived neural stem cells and induced neurons to study how an SVA insertion and a variable hexamer repeat change RNA splicing and reduce TAF1 expression. In lab models, removing the SVA with CRISPR rescued the transcriptional problems, and the renewed work will test antisense oligonucleotides (ASOs) to modulate TAF1. The goal is to turn these molecular findings into strategies that could eventually be developed into treatments.
Why it matters
Potential benefit: If successful, this work could lead to therapies that restore normal TAF1 function and slow or prevent neuron loss in people with XDP.
How similar studies have gone: Laboratory studies using patient-derived cells have shown that CRISPR removal of the SVA and early ASO approaches can reverse molecular defects, but clinical benefit in people has not yet been demonstrated.
Where this research is happening
-
Massachusetts General Hospital
Boston, United States Active
Researchers
- Principal investigator: Talkowski, Michael E — Massachusetts General Hospital
- Study coordinator: Talkowski, Michael E
Related research
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Role of THAP1 in brain cell support cells shaping brain development
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Leukocyte RNA biomarkers to help diagnose and monitor dystonia
A small study will look for RNA signatures in blood that could help diagnose and track dystonia in people who have the condition.
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Intrathecal baclofen for children with dystonia due to brain injury
A physician-led study at Baylor College of Medicine will help determine how ITB therapy affects daily life, comfort, and mobility for children with dystonia and related condition after brain injury.
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A researcher-led project uses mouse models to explore how a genetic change in DYT1 dystonia affects brain circuits and movement.
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Dystonia-specific brain signaling pattern in cerebellum
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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.