Gene-editing approaches for ACTA2-related blood vessel disease
Modeling and Therapeutic Approaches for Genetic Vasculopathies
This project works to create gene-editing therapies for children with the ACTA2 R179H mutation that causes strokes, weakened aortas, and other smooth muscle problems.
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-11169857 on NIH RePORTER |
What this research studies
From a patient point of view, the team is studying the exact ACTA2 R179H mutation in smooth muscle cells grown in the lab and in a new mouse model that mimics the human disease. They will look at how the mutation causes abnormal blood vessels, repeated strokes, and a weakened aorta, and they will track related behavior and neurologic outcomes in mice. To try to treat the disease they will use AAV delivery of CRISPR-based tools to either fix the mutation or disable the bad gene and check whether this improves blood vessel health and stroke outcomes before any human testing.
Who could benefit from this research
Good fit: Ideal candidates are children (and potentially adolescents) who carry the ACTA2 R179H mutation causing Smooth Muscle Dysfunction Syndrome, especially those with early strokes or aortic disease.
Not a fit: People without ACTA2 mutations or those whose organ damage is already advanced are unlikely to benefit from these preclinical therapeutic approaches in the near term.
Why it matters
Potential benefit: If successful, this work could lead to a gene therapy that reduces strokes, prevents life-threatening aortic problems, and improves long-term neurologic and respiratory outcomes for people with ACTA2 R179H.
How similar studies have performed: CRISPR and AAV-based gene therapies have shown promise in laboratory and early clinical work for some genetic diseases, but applying base-editing or gene-disruption to ACTA2 vascular disease is largely new and experimental.
Where this research is happening
Boston, United States
- Massachusetts General Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Musolino, Patricia L — Massachusetts General Hospital
- Study coordinator: Musolino, Patricia L
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.