A Comprehensive Monograph on Idursulfase (Elaprase®): Pharmacology, Clinical Efficacy, and Therapeutic Context in Mucopolysaccharidosis Type II

Executive Summary

Idursulfase, marketed under the brand name Elaprase®, represents a landmark achievement in the treatment of rare genetic disorders. As the first-in-class enzyme replacement therapy (ERT) for Mucopolysaccharidosis Type II (MPS II), or Hunter syndrome, it has fundamentally altered the clinical course for a generation of patients. Idursulfase is a recombinant form of the human lysosomal enzyme iduronate-2-sulfatase (I2S), produced in a human cell line to ensure structural and functional fidelity to the endogenous enzyme. Its mechanism of action is direct and intuitive: by providing an exogenous source of the deficient enzyme, it facilitates the catabolism of accumulated glycosaminoglycans (GAGs)—dermatan sulfate and heparan sulfate—within cellular lysosomes, thereby mitigating the systemic pathology of the disease.

Clinical trials have unequivocally demonstrated the somatic benefits of Idursulfase, most notably a significant improvement in physical endurance, as measured by the 6-minute walk test, and a reduction in organomegaly. These benefits have translated into a profound impact on the non-neurological aspects of Hunter syndrome, improving mobility and likely extending the lifespan of many patients. However, the therapeutic reach of Idursulfase is critically constrained by its molecular properties. As a large glycoprotein, it is unable to cross the blood-brain barrier (BBB), leaving the progressive and devastating neurological manifestations of severe Hunter syndrome untreated. This limitation is the single most important factor defining its clinical role and has become the primary driver for the development of next-generation therapies.