Alpha one antitrypsin deficiency: from gene to treatment.
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.
Wood
Alice M
AM
Department of Medical Sciences, University of Birmingham, Birmingham, UK.
Stockley
Robert A
RA
D015897:Comorbidity; D005541:Forced Expiratory Volume; D015316:Genetic Therapy; D014644:Genetic Variation; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000235:genetics; D012129:Respiratory Function Tests; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*