aln-aat

ALN-AAT is an investigational, subcutaneously administered RNA interference (RNAi) therapeutic developed to target alpha-1 antitrypsin (AAT) mRNA in hepatocytes. Its primary indication is the treatment of liver disease associated with alpha-1 antitrypsin deficiency (AATD), a genetic disorder that leads to the accumulation of misfolded AAT protein in the liver, causing cellular damage and progressive liver disease. ALN-AAT utilizes N-acetylgalactosamine-coupled small interfering RNA (siRNA) technology for targeted delivery and gene silencing at the mRNA level, resulting in potent and durable knockdown of serum AAT levels. Preclinical studies demonstrated robust reduction of mutant AAT protein, improvement in histopathology, reduced fibrosis, and decreased tumor formation in animal models. The drug was generally well tolerated in early clinical studies but development was discontinued due to transient increases in liver enzymes observed during trials[4][5][6].