New strategies for the treatment of lysosomal storage diseases

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders caused by the deficiency of any of the lysosomal functions, in most cases of lysosomal hydrolases. LSDs are typically characterized by storage of a variety of substrates in multiple tissues and organs and by the variable association of unusual clinical manifestations that are often responsible for physical and neurological handicaps. During the past two decades, research in the field of LSDs has made marked progress, particularly with the development of a variety of innovative therapeutic approaches. These include several strategies aimed at increasing the residual activity of the missing enzyme, such as hematopoietic stem cell transplantation, enzyme replacement therapy, pharmacological chaperone therapy and gene therapy. An alternative approach is based on reducing the synthesis of the stored substrate. More recently, the improved knowledge on LSD pathophysiology has indicated additional targets of therapy. The recent progress made in the treatment of LSDs represents a good model that may be extended to other genetic disorders.