Laronidase for the treatment of mucopolysaccharidosis type I

A decade has passed since the initial report that parenteral use of recombinant human α-L-iduronidase results in amelioration of symptoms in patients with mucopolysaccharidosis type I (MPS I). As a result, MPS I became the first mucopolysaccharide storage disorder to benefit from enzyme replacement therapy (ERT); subsequent ERTs have been approved for MPS II and VI. The ability of lysosomal storage disorders to respond to ERT is unique among genetic disorders and relates to the capability of cells to take up recombinant lysosomal enzymes through cell surface receptors and deliver them to the lysosome, a processed coined as 'cross-correction'. Although the concept of ERT is straightforward, the evaluation of its efficacy in disorders like MPS I is challenging. This article reviews the use of laronidase in the management of MPS I, with a particular emphasis on the unique issues inherent in the evaluation of therapeutics for such a rare, complex and progressive disorder.