Enzyme replacement and beyond

During the last decade, enzyme replacement therapy for lysosomal storage di seases became a reality with the demonstration of its safety and effectiven ess in type 1 Gaucher disease. Currently, enzyme replacement and several ot her potential therapeutic strategies are being developed for selected lysos omal storage diseases, including Fabry disease due to the deficient activit y of alpha -galactosidase A (alpha -Gal A). The development and clinical ev aluation of these new therapies require a stepwise process, each step being rigorously reviewed and approved by national or international regulatory a gencies. For lethal disorders that affect small populations, such as many i nherited metabolic diseases, this process can be accelerated by 'orphan dru g' and 'fast track' regulations. As an example of the drug development proc ess, the development of recombinant human alpha -Gal A (r-h alpha Gal A) re placement for Fabry disease is presented, including the preclinical studies in the 'Fabry mouse' model, and the clinical phase 1/2, phase 3, and phase 3 extension studies, which demonstrate the safety and efficacy of this new therapy.