Treatment of lysosomal storage disorders : progress with enzyme replacement therapy.

Enzyme replacement therapy (ERT) as treatment for lysosomal storage diseases (LSDs) was suggested as long ago as 1966 by De Duve and Wattiaux. However, it took >35 years to demonstrate the safety and effectiveness of ERT for type 1 Gaucher's disease. An important breakthrough was certainly the enactment of legislation in the US, designed to encourage commercialisation of products developed in academic institutions for pharmaceutical companies to invest in treatments for rare diseases. The principles elaborated in the development of the treatment of Gaucher's disease were subsequently applied to the development of ERT of other LSDs. The safety and effectiveness of ERT for Fabry's disease, mucopolysaccharidoses (MPS) I, MPS II and MPS VI, as well as for Pompe's disease have been demonstrated in well designed clinical trials, and the treatments are now commercially available throughout the world. Several questions remain to be answered. The long-term effectiveness of most of the treatments has not yet been established. What is reversible by ERT and what may not be reversible but is preventable, is not yet clear. The pathology in some tissues, such as the brain, is inaccessible to ERT, indicating that some manifestations of the LSD will not respond to the treatment. The extent of this problem is still unclear. The cost of ERT is very high, creating problems for third-party payers, which has strained reimbursement schemes based on the demonstration of acceptable cost effectiveness. ERT of LSDs represents the most important advance in the treatment of this class of diseases. The information that is currently being collected as part of large-scale observational studies will help to establish the full potential of the treatment.