AT2220 for Pompe Disease

AT2220 is an experimental, oral therapy for the treatment of Pompe disease and belongs to a class of molecules known as pharmacological chaperones.

Pompe Disease

Pompe disease, also known as glycogen storage disease type II or acid maltase deficiency, is a relatively rare neuromuscular and lysosomal storage disorder caused by inherited genetic mutations in a key enzyme called α-glucosidase (Gaa). Certain types of mutations cause changes that result in the production of Gaa with reduced stability that does not achieve its correct three-dimensional shape. The cell’s quality control mechanisms recognize and retain the misfolded Gaa until it is moved to another part of the cell for degradation and elimination. Consequently, little or no Gaa is able to reach the lysosome, where it normally breaks down glycogen, resulting in lysosomal glycogen accumulation in skeletal, cardiac, and smooth muscle tissues. Learn more about Pompe Disease . 

AT2220 for Pompe Disease

AT2220 is designed to act as a pharmacological chaperone by selectively binding to the misfolded enzyme responsible for Pompe disease, Gaa. After binding to the enzyme, it is thought that AT2220 promotes the proper folding, processing, and trafficking of the enzyme from the endoplasmic reticulum to its final destination, the lysosome, the area of the cell where the enzyme does its work. Once it reaches the lysosome, the pharmacological chaperone is displaced, and the enzyme can perform its normal function, which is the breakdown of its natural substrate, glycogen.

Clinical Progress

Amicus has conducted multiple preclinical studies in human cells from patients with Pompe disease in lab animals. AT2220 is currently in Phase 1 clinical trials  for the treatment of Pompe disease.