Iminosugars as active-site specific chaperones for the treatment of lysosomal storage disorders

CARB 33

Jian-qiang Fan, jian-qiang.fan@mssm.edu, Department of Human Genetics, Mount Sinai School of Medicine, 5th Avenue at 100th Street, New York, NY 10029
Imino sugars are proposed as small molecule drugs for the treatment of lysosomal storage disorders, such as Fabry disease and Gaucher disease. These compounds are potent competitive inhibitors of enzymes whose deficiency result in the diseases. At the sub-inhibitory concentrations, however, the imino sugars act as active-site specific chaperones (ASSCs) to induce or stabilize the proper conformation of the mutant enzyme, thus promoting the normal trafficking of the mutant enzyme through the ER secretory pathway, and ultimately increasing the residual enzyme activity in the lysosomes. Since these small molecules are likely to be orally active, they should have numerous advantages over enzyme replacement therapy, including easy accessibility to CNS, easy administration, greater affordability and convenience, provided they are non-toxic and can be demonstrated long-term safety.

 

Iminosugars: Therapeutic Potential
8:30 AM-12:10 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- 202A, Oral

Division of Carbohydrate Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005