A cure for alpha-1? Novel therapeutics in alpha-1 antitrypsin deficiency

Extract Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, that encodes alpha-1 antitrypsin (AAT) 1. AAT is an inhibitor of neutrophil serine proteases such as neutrophil elastase (NE) and proteinase-3 1. AATD is inherited in an autosomal co-dominant pattern, a homozygous mutation causes 95% of severe AAT deficiency involving a single amino acid substitution - Glu342Lys (referred to as the “Z” allele) 2. Approximately 1 in 25 individuals of Northern and Western European descent carry the Z allele, with lower frequencies reported in Southern Europe (1–2%) and rare occurrence in other populations 3.