Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin (AAT) deficiency is a rare genetic disorder that results in disease of the lungs and liver. AAT is a liver-produced serine proteinase inhibitor with the primary function of protecting the lungs from neutrophil elastase and other irritants that cause inflammation.
Mutations in AAT, most commonly in the “Z-allele” – Z-AAT – cause the protein to misfold, which hinders its normal release into the blood, thereby causing it to aggregate in hepatocytes, leading to liver injury, fibrosis, cirrhosis, and hepatocellular carcinoma. There are approximately 200,000 people in the U.S. and major European countries thought to be homozygous for the Z allele (PiZZ), and it is estimated that at least 10% have an associated liver pathology.
The only treatment options presently available for patients with cirrhosis caused by mutant AAT accumulation in the liver are supportive care and, in the case of advanced cirrhosis, liver transplantation. There exists a very high unmet need for therapies toward liver disease associated with AAT deficiency. RNAi-mediated inhibition of AAT in PiZZ patients may represent a promising new way to treat this rare disease.
ALN-AAT utilizes our proprietary Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform
enabling subcutaneous dosing with increased potency and durability, and a wide therapeutic index.
In June 2014, we entered into a collaboration with The Alpha-1 Project (TAP), the venture philanthropy subsidiary of the Alpha-1 Foundation, for the continued advancement of ALN-AAT. TAP’s mission is to work with patients, academia, pharmaceutical and biotech companies, and public health organizations in the pursuit of cures and therapies for chronic obstructive pulmonary disease (COPD) and liver disease caused by AAT deficiency. TAP is partially funding research activities for ALN-AAT.
Please read the latest press releases and data presentations for ALN-AAT here.