Chaperone therapy: Stabilization and enhancement of endogenous and exogenous lysosomal enzymes

Chaperone therapy is a new concept of molecular therapeutic approach to protein misfolding diseases, particularly to lysosomal diseases. Initially we started molecular analysis of culture cells, model animals and patients with Fabry disease and G_M1-gangliosidosis. Some mutant enzyme proteins did not express the catalytic activity because of unstable molecular structure in somatic cells. The small molecule compound (chaperone) corrected misfolding of the unstable mutant protein, resulting in restoration of the enzyme activity (chaperone therapy). This pathological molecular event was studied first in endogenous mutant enzymes. Then a similar molecular interaction was found between the chaperone and the exogenous protein supplied for enzyme replacement therapy (ERT) in Pompe disease. This new chaperone-ERT combination therapy will become another useful technology in order to expand the application of chaperone therapy to a wide range of lysosomal diseases. Thus, chaperone therapy is expected in future for stabilization and enhancement of exogenously supplied ERT enzymes as well as endogenous mutant enzymes.