Experimental and investigational drugs for the treatment of alpha-1 antitrypsin deficiency.

: Alpha-1 antitrypsin deficiency (AATD) is most often associated with chronic lung disease, early onset emphysema, and liver disease. The standard of care in lung disease due to AATD is alpha-1 antitrypsin augmentation but there are several new and emerging treatment options under investigation for both lung and liver manifestations. : We review therapeutic approaches to lung and liver disease in alpha-1 antitrypsin deficiency (AATD) and the agents in clinical development according to their mode of action. The focus is on products in clinical trials, but data from pre-clinical studies are described where relevant, particularly where progression to trials appears likely. : Clinical trials directed at lung and liver disease separately are now taking place. Multimodality treatment may be the future, but this could be limited by treatment costs. The next 5-10 years may reveal new guidance on when to use therapeutics for slowing disease progression with personalized treatment regimes coming to the forefront.