Stem cell-based therapy for lysosomal storage diseases

The family of lysosomal storage diseases (LSDs) affects 1 out of every 5,000-7,000 live births, and most affected LSD patients experience a rapidly progressive course after disease onset due to dysfunction of the lysosome. The brain is particularly sensitive to the abnormal storage of lysosomal aggregates, and lysosomal dysfunction in neurons and other cell types leads to the progressive degeneration of the central nervous system (CNS) in as many as 75% of all LSDs. Transplantation of stem cells has been studied for several LSDs due to the tremendous promise of these cells to deliver therapeutic gene products, sequester toxic compounds (e.g., accumulated metabolites), replace affected cells through engraftment and differentiation, and decrease inflammation in neurodegenerative disease states. This chapter describes the LSDs that have been tested using stem cell transplantation (SCT), and a review of the current state of LSD research is presented and highlights clinical improvements that have been reported.