Development of Fluorinated Carbohydrates for use as Positron Emission Tomography Imaging Agents and Pharmacological Chaperones in the Treatment of Lysosomal storage diseases

Lysosomal Storage Diseases (LSD) are a rare group of more than 40 disorders, including conditions such as Gauchers and Tay Sachs disease, in which a genetic abnormality leads to the buildup of naturally occurring compounds throughout the body. This process may lead to a variety of symptoms including skeletal defects, heart problems, mental retardation, and death. The diseases can be treated by enzyme replacement therapy, in which a missing enzyme is injected into the bloodstream so it can move into cells to alleviate the buildup of these compounds. However, the therapy is extremely expensive and cannot be used to alleviate neurological symptoms. Brian Rempel is developing imaging agents for Positron Emission Tomography (PET), a highly specialized technology that produces powerful images of the body's biological function. Using PET with enzyme replacement therapy would enable imaging of an injected enzyme and tailoring of the dose to the individual patient, which could reduce the costs of the therapy. As well, PET imaging would allow for a better understanding of how the enzyme is distributed throughout the body. Rempel is also investigating the development of pharmacological chaperones, molecules that bind to the mutant enzyme that is deficient in LSD patients. The molecules help the enzyme migrate to the correct cellular compartment where it can function normally, with the aim of enhancing the patient's own naturally occurring enzyme levels. Pharmacological chaperones would be a fraction of the cost of enzyme replacement therapy.