Targeting mutation hotspots in arrhythmogenic cardiomyopathy to guide new therapies
Pathogenic hotspots illuminate mechanism and therapeutic potential in arrhythmogenic cardiomyopathy
Looking at whether editing shared mutation 'hotspots' in two key heart genes can lead to new treatments for adults with genetic arrhythmogenic cardiomyopathy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Stanford University NIH-funded |
| Lab location | 1 site (Stanford, United States) |
| Project ID | NIH-11292395 on NIH RePORTER |
What this research studies
This project will map where harmful mutations cluster in two important heart genes (RBM20 and PKP2) and study how those hotspots cause arrhythmia and heart muscle disease. Researchers will use patient-derived heart cells, molecular studies of protein function, and genome-editing experiments to determine which variants act by loss of function versus dominant-negative effects. The team plans to design a single genome-editing reagent that could correct many different pathogenic variants located in the same hotspot. Work combines genetic analysis, cell-based models, and gene-editing methods to move toward therapies for patients with these variants.
Who could benefit from this research
Good fit: Adults diagnosed with arrhythmogenic cardiomyopathy who carry pathogenic variants in RBM20 or PKP2, or who can donate genetic samples, are the most relevant candidates for participation or follow-up trials.
Not a fit: Patients without a genetic cause for their cardiomyopathy, children, or those with unrelated heart conditions are unlikely to receive direct benefit from this project.
Why it matters
Potential benefit: If successful, this work could enable gene-editing treatments that correct many harmful variants in arrhythmogenic cardiomyopathy and lower the risk of arrhythmia and heart failure.
How similar studies have performed: Early genome-editing efforts for heart disease have shown promise for gene replacement, but approaches aimed at dominant-negative variants are newer and less tested.
Where this research is happening
Stanford, United States
- Stanford University — Stanford, United States (Active)
Researchers
- Principal investigator: Parikh, Victoria — Stanford University
- Study coordinator: Parikh, Victoria
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.