Fixing Factor VIII misfolding to make hemophilia A gene therapy safer
Overcoming FVIII protein misfolding and cell toxicity
This project aims to help Factor VIII fold and leave liver cells properly so AAV gene therapy for people with hemophilia A works longer and with less liver damage.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Indiana University Indianapolis NIH-funded |
| Lab location | 1 site (Indianapolis, United States) |
| Project ID | NIH-11325359 on NIH RePORTER |
What this research studies
Researchers are working to improve AAV gene therapy that delivers Factor VIII to liver cells for people with hemophilia A. They study why Factor VIII misfolds, forms toxic aggregates in the endoplasmic reticulum, and triggers liver stress and inflammation. The team tests modified FVIII designs and cellular helper strategies in the lab and preclinical models to boost secretion, reduce aggregation, and lower the vector dose needed. Their goal is steadier clotting factor levels and less liver injury after gene therapy.
Who could benefit from this research
Good fit: People with moderate-to-severe hemophilia A, including men and affected women/carriers with low FVIII levels who are considering or eligible for gene therapy, would be the main candidates.
Not a fit: People with other bleeding disorders, those ineligible for AAV-based approaches (for example due to pre-existing anti-AAV antibodies or advanced liver disease), or those not considering gene therapy may not benefit from this work.
Why it matters
Potential benefit: If successful, this could enable safer, lower-dose AAV gene therapy that provides longer-lasting clotting factor levels for people with hemophilia A.
How similar studies have performed: Previous AAV-FVIII gene therapy trials have reduced bleeding for many patients but sometimes required very high doses and showed waning expression or liver inflammation, so this work builds on those results to solve protein-level problems.
Where this research is happening
Indianapolis, United States
- Indiana University Indianapolis — Indianapolis, United States (Active)
Researchers
- Principal investigator: Kaufman, Randal J. — Indiana University Indianapolis
- Study coordinator: Kaufman, Randal J.
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.