indication

For the treatment of adults and children with Mucopolysaccharidosis VI.

pharmacology

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG. Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the accumulation of the GAG substrate dermatan sulfate, throughout the body. This accumulation leads to widespread cellular, tissue, and organ dysfunction. Galsulfase is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG. Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors.

mechanism of action

Galsulfase supplies recombinant-engineered galsulfase, a normal variant form of the polymorphic human enzyme, N-acetylgalactosamine 4-sulfatase. It is a lysosomal hydrolase that catalyzes the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of GAG chondroitin 4-sulfate and dermatan sulfate. Increased catabolism of GAG in turn reduces systemic dermatan sulfate accumulation, thereby reducing the primary symptoms of MPS VI.

toxicity

There is no experience with overdose of galsulfase.

half life

9 (6 to 21) minutes during the first week of treatment, 26 (8 to 40) minutes by the 24th week.