Augmentation therapy with alpha 1-antitrypsin: present and future of production, formulation, and delivery.

Alpha 1-antitrypsin is one of the first protein therapeutics introduced on the market - more than 30 years ago - and, to date, it is indicated only for the treatment of the severe forms of a genetic condition known as alpha-1 antitrypsin deficiency. The only approved preparations are derived from plasma, posing potential problems associated with its limited supply and high processing costs. Moreover, augmentation therapy with alpha 1-antitrypsin is still limited to intravenous infusions, a cumbersome regimen for patients. Here, we review the recent literature on its possible future developments, focusing on i) the recombinant alternatives to the plasma-derived protein, ii) novel formulations, and iii) novel administration routes. Regulatory issues and the still unclear noncanonical functions of alpha 1-antitrypsin - possibly associated with the glycosylation pattern found only in the plasma-derived protein - have hindered the introduction of new products. However, potentially new therapeutic indications other than the treatment of alpha-1 antitrypsin deficiency might open the way to new sources and new formulations.