Téma: Review papers

Lysosomal storage diseases: enzyme replacement therapy

Vladimír Bzdúch, Darina Behúlová

Lysosomal storage disorders are a group of hereditary metabolic disorders that are most often caused by reduced or absent activity of specific lysosomal enzymes. Approximately fifty diseases have been describe to date. The classification as lysosomal storage diseases had to await the discovery of lysosomes by Christian de Duve in 1955 and the development of the concept of lysosomal diseases by Hers in 1965. In many of the diseases, however, the storage material was already identified long before lysosomes were discovered (Tay-Sachs disease, Gaucher disease, Fabry disease). Enzyme replacement therapy (ERT), which means administration of the resposible enzyme to the patients, was proposed by de Duve in 1964 and became a reality in early 1990s, when purified glucocerebrosidase derived from human placenta could be targeted to phagocyte-macrophage system. ERT for non-neuronopathic Gaucher disease has been a great success because its safe and high effectiveness and led to attempt to use ERT in the other lysosomal disease. But ERT has also showen some limits mainly in terms of tissue distribution and difficulty in delivering therapeutic agents across the blood-brain barrier with no effectivity on neurological manifestation. Currently, ERT has been approved for six lysosomal storage diseases: Gaucher disease type I, Fabry disease, mucopolysaccharidosis I, II and VI and Pompe disease. Despite many open and unsolved questions, ERT of lysosomal diseases ranks among the big medical success in twentieth century.