Chaperone Therapy

Pharmacological or molecular chaperone therapy is among the newest therapeutic ideas for lysosomal storage diseases. Pharmacological chaperones are small molecules that specifically bind to and stabilize the functional form or three-dimensional shape of a misfolded protein in the endoplasmic reticulum (ER) of a cell. When misfolded due to a genetic mutation, the protein (Enzyme) is unable to adopt the correct functional shape. This misfolded protein is recognized by the quality control system in the cell, and destroyed, leading to decreased amounts of enzyme that gets transported from the cell’s ER to the cell’s lysosome resulting in reduced enzyme activity. The binding of the chaperone molecule helps the protein fold into its correct three-dimensional shape. This allows the protein to be properly trafficked from the ER and distributed to the lysosome in the cell, which would increase enzyme activity and cellular function, and reduce substrate and stress on the cells. As of summer 2006, pharmacological chaperone therapy is in early stage clinical trials for lysosomal storage diseases Fabry and Gaucher Type I. To learn more on this mechanism of action visit