Alpha-1 antitrypsin augmentation therapy

COPD. 2013 Mar:10 Suppl 1:64-7. doi: 10.3109/15412555.2013.764402.

Abstract

The therapy of alpha-1 antitrypsin deficiency (AATD) is an example of a medical triumph over a common hereditary disease. Based on the understanding of the pathogens of the disease as a deficiency in liver production of alpha-1 antitrypsin (AAT) resulting from inherited genetic variation in both parental AAT genes, the knowledge that A1AT functions primarily to inhibit neutrophil elastase (NE), and the observation that NE instilled into the lung of experimental animals resulted in emphysema, the concept evolved that the pulmonary manifestations of the disease could be halted by intermittent intravenous infusions of AAT purified from pooled human plasma. Following preliminary clinical studies in the academic community, and then pharmaceutical company development of large scale purification of human AAT, the FDA approved the use of weekly AAT augmentation therapy for AATD following a clinical trial which demonstrated that weekly infusions would raise to normal plasma and lung epithelial fluid levels of AAT in AAT-deficient individuals. The therapy is now used worldwide to treat AATD, the only pulmonary genetic disease with effective therapy for all affected individuals.

Publication types

  • Review

MeSH terms

  • Evidence-Based Medicine
  • Humans
  • Registries
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / therapeutic use*
  • alpha 1-Antitrypsin / administration & dosage
  • alpha 1-Antitrypsin / therapeutic use*
  • alpha 1-Antitrypsin Deficiency / drug therapy*
  • alpha 1-Antitrypsin Deficiency / enzymology

Substances

  • Serine Proteinase Inhibitors
  • alpha 1-Antitrypsin