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Enzyme replacement and beyond
Author(s) -
Desnick R. J.
Publication year - 2001
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1010331404448
Subject(s) - enzyme replacement therapy , fabry disease , lysosomal storage disease , orphan drug , medicine , alpha galactosidase , disease , drug development , substrate reduction therapy , drug , lysosomal storage disorders , pharmacology , drug discovery , intensive care medicine , bioinformatics , biology
During the last decade, enzyme replacement therapy for lysosomal storage diseases became a reality with the demonstration of its safety and effectiveness in type 1 Gaucher disease. Currently, enzyme replacement and several other potential therapeutic strategies are being developed for selected lysosomal storage diseases, including Fabry disease due to the deficient activity of α‐galactosidase A (α‐Gal A). The development and clinical evaluation of these new therapies require a stepwise process, each step being rigorously reviewed and approved by national or international regulatory agencies. For lethal disorders that affect small populations, such as many inherited metabolic diseases, this process can be accelerated by ‘orphan drug’ and ‘fast track’ regulations. As an example of the drug development process, the development of recombinant human α‐Gal A (r‐hαGal A) replacement 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.