Alpha one antitrypsin deficiency: from gene to treatment

Respiration. 2007;74(5):481-92. doi: 10.1159/000105536.

Abstract

Alpha1-antitrypsin deficiency is a genetic disorder which contributes to the development of chronic obstructive pulmonary disease, bronchiectasis, liver cirrhosis and panniculitis. The discovery of alpha1-antitrypsin and its function as an antiprotease led to the protease-antiprotease hypothesis, which goes some way to explaining the pathogenesis of emphysema. This article will review the clinical features of alpha1-antitrypsin deficiency, the genetic mutations known to cause it, and how they do so at a molecular level. Specific treatments for the disorder based on this knowledge will be reviewed, including alpha1-antitrypsin replacement, gene therapy and possible future therapies, such as those based on stem cells.

Publication types

  • Review

MeSH terms

  • Comorbidity
  • Forced Expiratory Volume
  • Genetic Therapy
  • Genetic Variation
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Emphysema / genetics
  • Respiratory Function Tests
  • alpha 1-Antitrypsin Deficiency / complications
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / genetics*
  • alpha 1-Antitrypsin Deficiency / therapy*