Marco De Giorgi, PhD

Pilot Research Award
$50,000 over one year

Baylor College of Medicine

In vivo expansion of gene-targeted hepatocytes as a treatment for alpha-1 antitrypsin deficiency

The liver produces most of the proteins that circulate in the bloodstream. Among these, alpha-1 antitrypsin (AAT) is important for protecting the lungs from environmental hazards, like pollution and smoking. There is a rare genetic disease - alpha-1 antitrypsin deficiency (AATD) - where the liver produces a wrong variant of AAT (named as Z-AAT). The Z-AAT variant is not released in the bloodstream and accumulates in the cells of the liver, eventually causing liver damage. In addition, AATD patients also develop lung disease due to the absence of protective levels of AAT in circulation. There is not actual cure for AATD. My project aims at developing a novel treatment for AATD. My therapeutic strategy consists in eliminating the Z-AAT variant, and instructing the liver to produce the healthy version of AAT and release it in circulation. To do so, I will produce therapeutic viruses and test them in laboratory mice that mimic the human AATD disease.  These viruses will go to the liver and correct a fraction of cells. Then, I will selectively expand the corrected cells for increasing the production of healthy AAT. I expect that my strategy will rescue the liver and lead to the production of AAT levels required for lung protection.