Alpha1-antitrypsin deficiency (AATD) is an autosomal co-dominant condition characterised by low circulating levels of Alpha1-antitrypsin (AAT) and the accumulation of polymerised AAT molecules in the hepatocyte. Patients with this condition are susceptible to developing chronic lung and liver disease. Lung disease occurs in part from loss of neutrophil elastase inhibition and liver disease from a gain-of-toxic function and endoplasmic reticulum stress in hepatocytes. The pro-inflammatory nature of AAT polymers likely contributes to disease pathogenesis. New therapeutic efforts are being developed targeting specific pathophysiology mechanisms of the disease. These include increasing circulating AAT levels above the current therapeutic target with higher doses of intravenous AAT or by direct administration to the lung via the inhaled route. Other efforts include gene therapy and development of strategies to decrease the intracellular accumulation of AAT polymers by enhancing cellular degradation mechanisms, using chemical chaperones to target protein misfolding and designing molecules that can act as blockers of AAT polymerisation.
|Original language||English (US)|
|Number of pages||5|
|Journal||European Respiratory Disease|
|State||Published - Sep 1 2011|
- Alpha1-antitrypsin deficiency
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine