Efficacy and safety of enzyme replacement therapy for MPS I with 100 I.U./Kg recombinant human a-L-iduronidase (ALDURAZYME™).

Mucopolysaccharidose type I (MPS I) is caused by the deficiency of the lysosomal enzyme a-L-Iduronidase.

Due to this deficiency heparan sulphate and dermatan sulphate (glycosaminoglycans, GAGs) accumulate in the lysosomes of all cells, but predominantly in the connective tissue.
Clinical features encompass a spectrum of disease manifestations.

Three phenotypes are recognized;

1. the neuronopathic (Hurler) type at one end of the spectrum;

2. an intermediate (Hurler-Scheie) phenotype;

3. and a non-neuronopathic (Scheie) phenotype at the far end of the spectrum.

In both the non-neuronopathic and neuronopathic forms, visceral complications occur, such as joint abnormalities, hepatomegaly, cardiac valve abnormalities, skeletal abnormalities and corneal clouding.

The most severe expression of the disease is found in the neuronopathic form; here visceral symptoms occur very early in life, with concomitant devastating, irreversible central nervous system involvement, giving rise to considerable morbidity from a very early age onwards and death on average around the 5th year of age.

In the Scheie phenotype psychomotor development is normal. Skeletal and joint manifestations form the important disease burden in these patients.

Recently, trials with weekly a-L-Iduronidase (Aldurazyme™, Genzyme/Biomarin) infusions showed improvement in joint mobility, lung function and exercise tolerance, as determined by the 6 minute walk test. Aldurazyme™ received marketing approval as an orphan drug from the EMEA in April 2003.

However, there are still many open issues regarding the efficacy of treatment, making uniform evaluation of treatment in selected groups of MPS I patients mandatory.

MPS I patients can be treated with Aldurazyme safely and effectively.

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Enzyme replacement therapy with Aldurazyme.