Idursulfase: enzyme replacement therapy for mucopolysaccharidosis Type II (Hunter syndrome)

Abstract

Mucopolysaccharidosis type II (Hunter syndrome) is a lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase leading to tissue accumulation of glycosaminoglycans. It manifests with short stature, joint stiffness, coarse facial features, hepatosplenomegaly, and progressive mental retardation. Most children die in the first or second decade from pulmonary or cardiac involvement. Until recently, no specific treatment was available. A Phase II/III trial of idursulfase, a recombinant enzyme replacement therapy for this disorder, demonstrated significant improvement in a 6-min walk test and in pulmonary function tests, and a decrease in liver and spleen size among those receiving active therapy once weekly. Major side effects include allergic reactions, which generally are easily managed and do not require discontinuing therapy. Idursulfase is now approved in the US, and should provide significant improvement in quality of life for these individuals. This article reviews the disease and treatment, with comments on future therapeutic directions.

Keywords::

• genetics
• inborn errors of metabolism
• lysosomal storage disease
• orphan drug
• pharmacology
• therapeutics