Advances in the treatment of alpha1-antitrypsin deficiency

Jorge Lascano, Matthias Salathe, Michael Campos

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish (US)
Pages (from-to)122-126
Number of pages5
JournalEuropean Respiratory Disease
Volume7
Issue number2
StatePublished - Sep 1 2011

Keywords

  • Alpha1-antitrypsin
  • Alpha1-antitrypsin deficiency
  • Treatment

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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