Development of a long-acting version of Alpha1 antitrypsin for augmentation therapy in Alpha1 antitrypsin deficiency
(2022)
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- Authors
- Supervisors
- Vanbever, Rita
- Abstract
- Alpha-1 antitrypsin (AAT) is a serine protease inhibitor. A low level of serum AAT (<11 µM) is defined as AAT deficiency. The limitations of the current treatments for AAT deficiency-related lung disease are the low AAT lung penetration rate following intravenous infusion and the rapid AAT clearance from the lung following inhalation. Here, we present a PEGylated version of AAT, which shows improved resistance to proteolysis in vitro. In vivo, PEGylated AAT exhibits prolonged body residency after delivery by the intravenous and intratracheal routes. In a murine COPD model, a low intranasal dose of PEGylated AAT achieves better efficacy than a 45-fold higher intravenous dose of AAT. PEGylated AAT represents a promising alternative for AAT augmentation therapy.
- Affiliations
Citations
Liu, X. (2022). Development of a long-acting version of Alpha1 antitrypsin for augmentation therapy in Alpha1 antitrypsin deficiency. https://hdl.handle.net/2078.5/108605