Cipaglucosidase alfa (Pombiliti)

概览

Cipaglucosidase alfa is a recombinant human acid alpha-glucosidase used to treat late-onset Pompe disease in adults.

作用机制

Pompe disease, also known as glycogen storage disease type II (GSD II), is a rare inherited disorder caused by alpha-glucosidase (GAA) gene mutations. In normal conditions, GAA hydrolyzes glycogen and releases free glucose units in lysosomes. However, patients with Pompe disease have a GAA deficiency, and glycogen accumulates within lysosomes, impairing the function of smooth, cardiac, and skeletal muscle cells and causing tissue damage. Cipaglucosidase alfa is a recombinant form of GAA conjugated with mannose-6-phosphate (M6P) N-glycans. Attributing to M6P, cipaglucosidase alfa has a high affinity for the cation-independent mannose-6-phosphate receptor (CI-MPR), a receptor responsible for the transport of GAA to lysosomes. Upon binding to CI-MPR, cipaglucosidase alfa is internalized by the lysosomes and undergoes proteolytic cleavage and N-glycan trimming to form the mature and active form of the GAA enzyme to cleave glycogen. Cipaglucosidase alfa is coadministered with miglustat, which stabilizes the conformation of the enzyme.

适应症

In Europe, cipaglucosidase alfa is a long-term enzyme replacement therapy used in combination with the enzyme stabilizer miglustat for the treatment of adults with late-onset Pompe disease, also known as acid α-glucosidase (GAA) deficiency.

• Late-onset Pompe Disease