Description
Mucopolysaccharidosis I (MPS I) is a rare genetic lysosomal storage disease caused
by the deficiency of a-L-iduronidase, an enzyme required for the catabolism of
dermatan sulfate and heparin sulfate. The deficiency blocks the degradation of these
mucopolysaccharides, which accumulate in a variety of tissues including liver,
spleen, heart and connective tissues. The clinical manifestations of MPS I can
include progressive developmental delay, airways obstruction, hepatosplenomegaly,
severe joint restriction and cardiovascular disease. There are three subtypes of MPS I
depending on its clinical severity: Hurler’s syndrome (severe), Hurler-Scheie
syndrome (moderate), and Scheie syndrome (mild). Among the existing therapies,
bone marrow transplantation has been the only effective option for Hurler’s
syndrome. Laronidase was launched as an enzyme replacement therapy for
the treatment of patients with Hurler and Hurler-Scheie syndromes and patients with
the Scheie syndrome who have moderate to severe symptoms. It is a recombinant
form of the human a-L-iduronidase produced by overexpression in a Chinese hamster
ovary cell line. The recommended dosage regimen of laronidase is 0.58 mg/kg of
body weight administered once weekly as an intravenous infusion. The efficacy of
laronidase was demonstrated in a 26-week, double-blind, placebo-controlled clinical
trial by measuring improvement in pulmonary function and endurance. The
laronidase-treated patients showed a mean increase of 4.0% in predicted forced
vital capacity (FVC) and a mean increase of 38.0 m in the distance walked in 6 min
as compared with placebo-treated patients. Reductions in liver size and in urinary
glycosaminoglycan excretion were also observed. The most common adverse events
associated with laronidase were upper respiratory tract infection, rash and injection site reaction.
