Project Summary: This study focuses on the development of a novel way to perform enzyme replacement therapy and its application to MPS IIIA. In this method, the missing enzyme is produced in cells, purified and then attached to a small chemical entity that acts as a carrier. Previous work has shown that cells derived from MPS IIIA patients take up conjugated enzyme and that intravenous injection of modified enzyme reduces storage of glycosaminoglycans (GAGs) in a mouse model of MPS IIIA (Sgsh-/- ). Unexpectedly, intranasal administration of modified enzyme demonstrated high levels of delivery to the brain and reduction of pathological GAGs in a short-term experiment.
The purpose of this study is to optimize the transfer of enzyme into the central nervous system in the MPS IIIA mouse. The results will provide the pre-clinical information needed to proceed towards a novel treatment of the disease in humans.
Dates: October 2015 – September 2016
Update – April 2017: An improved enzyme assay has been created to more reliably evaluate the activity levels in organs, earliest safe age of administration in animal model has been established, long term dosing study is underway. Manuscript has been submitted for publication on GNeo carrier conjugation with enzyme (MPSI and early MPSIIIA work).