Treating alpha-1 antitrypsin deficiency by targeting cellular protein-folding pathways
Managing Alpha-1-Antitrypsin Deficiency (AATD) through Proteostasis Signaling Pathways
This project uses small molecules to fix how cells fold alpha-1 antitrypsin so people with different genetic forms of alpha-1 antitrypsin deficiency may keep healthier livers and lungs.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Scripps Research Institute, the NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11285254 on NIH RePORTER |
What this research studies
I have alpha-1 antitrypsin deficiency when my body makes a misfolded AAT protein that can build up in the liver and fail to protect the lungs. Researchers are studying the cell's protein‑folding machinery (including ATF6 and IRE1/XBP1s and chaperones like Hsp70/Grp78 and Hsp90/Grp94) to see if small molecules can reduce harmful AAT aggregation and restore normal protein function. They will test many different genetic AAT variants to find which pathways and compounds work best for each variant using laboratory models and human-derived samples. The ultimate aim is to match treatments to a person’s specific AAT variant to slow or prevent liver and lung damage.
Who could benefit from this research
Good fit: People diagnosed with alpha-1 antitrypsin deficiency, especially those with known AAT gene variants or early signs of liver or lung disease, would be the most relevant candidates.
Not a fit: People without AAT deficiency, those with end-stage irreversible organ damage, or individuals whose specific AAT variants do not respond to proteostasis-targeting drugs may not benefit from this approach.
Why it matters
Potential benefit: If successful, this work could lead to medicines that lower liver AAT buildup and preserve lung function for people with AAT deficiency.
How similar studies have performed: Laboratory studies have shown that modulating proteostasis pathways can reduce protein misfolding in models, but using small molecules across diverse human AAT variants for patient benefit remains largely experimental.
Where this research is happening
La Jolla, United States
- Scripps Research Institute, the — La Jolla, United States (Active)
Researchers
- Principal investigator: Balch, William Edward — Scripps Research Institute, the
- Study coordinator: Balch, William Edward
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.