Enzyme replacement therapy: from concept to clinical practice

Abstract

In the early 1960s, the first lysosomal storage disease was identified. Since then over 40 such diseases have been reported. The common feature is that enzyme deficiency leads to accumulation of undegraded macromolecules and lysosomal engorgement, resulting in organ dysfunction. Enzyme replacement therapy (ERT) is being developed for many of these disorders. The present paper summarizes the history of the development of ERT, with particular reference to the mucopolysaccharidoses, and specifically, to mucopolysaccharidosis type VII (MPS VII). The rarity of MPS VII has meant that ERT is not yet available for the small number of affected patients, although the study of MPS VII and murine models of the disease have played an important part in the development of treatment for related disorders, including Gaucher disease.

Conclusion: Much progress has been made in our understanding of lysosomal storage diseases over the past 40 years. This has led to the development of effective ERT for some of the more common storage diseases, such as Fabry disease and Gaucher disease. Treatment is still awaited, however, for many of the other rare disorders in this area, such as MPS VII.