Aralast: an α₁-protease inhibitor for the treatment of α-antitrypsin deficiency

Abstract

α-Antitrypsin (AAT) is a serine protease inhibitor, which inhibits the proteolytic enzyme elastase. Individuals with a deficiency of AAT may develop clinical manifestations that include a decline in lung function. Deficiency of AAT can lead to many clinical manifestations, most commonly chronic obstructive pulmonary disease in the form of emphysema. However, patients with this genetic disorder may also develop dysfunctions of other organs such as the liver and/or skin. There are ∼ 100 alleles associated with the gene encoding for AAT, where the estimated prevalence of this disorder is approximately as common as cystic fibrosis; however, misdiagnosis continues to be a problem. Augmentation therapy using intravenous AAT has been shown to reduce the forced expiratory volume in one second decline, associated with AAT deficiency. Restoration of serum AAT concentrations above 11 μM have correlated with a reduced level of disease progression. The normal dosing regimen of intravenous AAT is 60 mg/kg given every week. Although a dosage consolidation of 250 mg/kg given every 28 days has been explored, long-term efficacy has not been determined. Aralast is one of three approved human plasma-derived treatment options used to prevent the progression of emphysema associated with AAT deficiency disorder.

Keywords::

• α-antitrypsin deficiency
• α₁-antitrypsin