Pegunigalsidase alfa

Fabry disease is an X-linked recessive disorder caused by mutations in the GLA gene that lead to the loss of function of α-galactosidase A. This α-galactosidase A deficiency leads to the accumulation of globotriaosylceramide (GB3) and other neutral glycosphingolipids throughout the body, including the heart, kidney, nervous system, vascular endothelium and smooth muscle. This accumulation of GB3 is characterized by chronic pain, ocular opacities, liver and kidney impairment, skin lesions, vascular deterioration and cardiac deficiencies.

Pegunigalsidase alfa is a pegylated recombinant form of human α-galactosidase-A, with an amino acid sequence similar to the human enzyme that replaces α-galactosidase-A. It promotes the hydrolysis of the terminal α-galactosyl moieties of oligosaccharides and polysaccharides in the lysosome, reducing the amount of GB3 accumulated in patients with Fabry disease. The deacylated form of GB3, globotriaosylsphingosine (lyso-GB3), also plays a role in the development of Fabry disease, and the use of pegunigalsidase alfa decreases the accumulation of this metabolite as well.