Emerging drugs for alpha-1-antitrypsin deficiency

Robert Stockley

Research output: Contribution to journalArticle

10 Citations (Scopus)


IMPORTANCE OF THE FIELD Alpha-1-antitrypsin (A1AT) deficiency is a common genetic condition that predisposes individuals to the development of chronic obstructive pulmonary disease (COPD) as a direct result of damage caused to the lung by proteolytic enzymes released by migrating neutrophils. The lack of A1AT fails to control these enzymes and in the most common genetic deficiency (Pi Z) is due to accumulation of A1AT in the liver as a result of polymer formation. There is no specific treatment for COPD but understanding the pathophysiology of the disease in A1AT deficiency has led to strategies being used or developed to prevent the lung and liver disease. These strategies may have benefits beyond A1AT deficiency. AREAS COVERED IN THIS REVIEW The review covers the history of discovery of the nature and role of A1AT deficiency with particular emphasis on the pathophysiology of the lung disease. Evidence for the role of current therapies is provided together with data of preliminary or experimental strategies that are under development. WHAT THE READER WILL GAIN The reader will gain insight into the role of proteinases in the pathophysiology of COPD with particular reference to A1AT deficiency, which is the only human model of the disease. Current evidence of the efficacy of augmentation is provided together with new ways of readdressing the balance between neutrophil proteinases and natural or synthetic inhibitors or repairing lung damage. TAKE HOME MESSAGE A1AT deficiency is a good model to investigate the role of inflammation and proteolytic enzymes in the pathophysiology of COPD. Augmentation therapy is expensive but restores the deficiency to normal and current evidence suggests this ameliorates progression of the disease. Understanding the mechanisms involved has led to the development of newer strategies to protect the lung and liver from the development of disease but efficacy and safety concerns require careful introduction of these strategies. Although the condition is relatively common in the Northern hemisphere, the ability to deliver conventional Phase III clinical trials with lung physiology as the primary outcome will be limited by the sensitivity of the tests and number of patients required.
Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalExpert Opinion on Emerging Drugs
Publication statusPublished - 18 Aug 2010


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