Small molecules to repair misfolded cornea proteins in endothelial dystrophy
Analysis of chemical modulators for corneal endothelial dystrophies
Testing small drug-like molecules to help faulty SLC4A11 proteins work properly for people with corneal endothelial dystrophies like Fuchs disease.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11142548 on NIH RePORTER |
What this research studies
This project searches for small molecules that help the SLC4A11 protein fold correctly in corneal endothelial cells because misfolding of this protein causes several corneal endothelial dystrophies. Researchers run high-throughput chemical screens and cell-based assays to find compounds that restore the mutant protein's function in lab models. Promising compounds are followed up with more detailed laboratory tests of activity and safety, building on prior work that found one compound (glafenine) could correct folding in cells but is unsafe for patients. The long-term aim is to develop safe medicines that could improve corneal cell health and reduce the need for transplantation.
Who could benefit from this research
Good fit: People with corneal endothelial dystrophies caused by SLC4A11 mutations — for example Fuchs endothelial corneal dystrophy, CHED, or Harboyan syndrome — would be the most relevant candidates.
Not a fit: Patients whose corneal disease is due to other genetic causes or who already have advanced scarring or have received a transplant are unlikely to benefit from this approach.
Why it matters
Potential benefit: Could produce first-in-class drugs that restore corneal endothelial function, improve vision, and reduce reliance on corneal transplant surgery.
How similar studies have performed: Laboratory studies have shown proof-of-concept—one compound (glafenine) corrected SLC4A11 folding in cells—but that compound is unsafe for clinical use and safe clinical candidates remain unproven.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Chan, Matilda F — University of California, San Francisco
- Study coordinator: Chan, Matilda F
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.