11 - Cell therapy for peripheral diseases and reconstructive applications: Transplants for lysosomal storage disease

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All lysosomal storage disease (LSDs) are inherited as autosomal recessive except for three X-linked diseases: Fabry disease, mucopolysaccharidosis, and Danon disease. Most, but not all, of the lysosomal enzymes are localized in the lysosome via mannose 6-phosphate receptor (M6PR) mediated transport from the trans-Golgi network. A part of the lysosomal enzyme is excreted outside the cell and taken up by other cells via M6PR on the cell surface and subsequently localized in the lysosome. This phenomenon is called cross collection, which provides a rationale for developing clinical strategies to treat these diseases using bone-marrow transplantation (BMT) and enzyme replacement therapy (ERT). The rationale of using BMT for the treatment of LSD is that the transplanted hematopoietic stem cells can differentiate into their progeny and then be distributed throughout the whole body. The new hematopoietic cells can then secrete the missing enzymes and are subsequently taken up by the neighboring cells. The identification of hematopoietic cells in the brain as microglia provides further evidence that the BMT can be effective for neurological involvement. ERT is available for Gaucher disease, Fabry disease, and MPS I. ERT is currently being developed for Pompe, mucopolysaccharidosis type II, Niemann-Pick B, and MPS VI.