Development of Small molecular pharmacological chaperone therapy for lysosomal storage diseases

Abstract

Lysosomal storage diseases are a group of metabolic diseases, caused by genetic deficiency of lysosomal hydrolase enzymes or their co-factors, that results in progressive accumulation of undigested lipids or glycolipids in the lysosomes of affected cells. Chaperone compounds bind to and stabilize the mutant enzyme protein and enhanced their residual activity in the patients’ cells. Initial development of this therapy was conducted in Japan. Small molecular chaperone compounds can be orally administered and can attenuate neurological manifestations. In this essay, I would like to describe our development of candidate chaperone compounds and the recent clinical applications of this therapy.