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Enzyme replacement therapy and beyond—in memoriam Roscoe O. Brady, M.D. (1923–2016)
Author(s) -
Ries Markus
Publication year - 2017
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 - 10.1007/s10545-017-0032-8
Subject(s) - substrate reduction therapy , lysosomal storage disease , enzyme replacement therapy , lysosomal storage disorders , fabry disease , orphan drug , drug discovery , drug development , medicine , milestone , disease , batten disease , drug , clinical trial , bioinformatics , pharmacology , biology , pathology , history , archaeology
Lysosomal storage disorders are strong candidates for the development of specific innovative therapies. The discovery of enzyme deficiencies is an important milestone in understanding the underlying cause of disease. Being able to replace the first missing enzyme in a lysosomal storage required three decades of dedicated research. Successful drug development for lysosomal storage disorders was fostered by the U.S. Orphan Drug Act. Various optimization strategies have the potential to overcome the current limitations of enzyme replacement therapies. In addition, substrate reduction therapies are an alternative approach to treat lysosomal storage disorders, chemical chaperones enhance residual enzyme activity, and small molecules can facilitate substrate transport through subcellular compartments. Bone‐marrow derived multipotent stem cells and gene therapies have received FDA orphan drug designation status. The science of small clinical trials played an essential role: non‐neurological endpoints, biomarker, and regulatory alignment are key factors in successful drug development for lysosomal storage disorders. Being able to treat brain disease is the next frontier. This review is dedicated to the memory of Roscoe O. Brady, an early pioneer in the research of lysosomal storage diseases.