New Therapy for Six Mucopolysaccharidoses

Cure Sanfilippo Foundation is co-funding this project in Collaboration with Sanfilippo Children’s Foundation (Australia).

Project Summary: Substrate reduction therapy by targeting the N-deacetylase/N-sulfotransferase (NDST) isozymes, NDST1, represents a promising approach to developing a therapy for multiple MPS disorders including MPS I, MPS II, MPS IIIA, MPS IIIC, MPS IIID, MPS IIIE.  One of the advantages of such small molecule therapy is the likely ability of the molecules to pass through the blood-brain barrier and thus treating the disease in the brain. It provides a potential strategy to enhance effectiveness of emerging therapies, i.e. enzyme replacement and gene delivery approaches, and it offers treatments for almost all disease sub-types. 

This study aims to decrease the synthesis of glycosoaminoglycans (GAGs) by targeting NDST1, a key enzyme in the pathway leading to modifications of heparan sulfate.  This project will screen a library of 6,000 compounds to identify drugs that reduce NDST1 activity by two independent approaches; via repression of NDST1 gene expression or via direct inhibition of NDST1 enzyme activity

Repurposing of approved drugs will be prioritized in this research for faster transition of drug candidates into clinical studies. The hospital’s CRISPR approach enables testing drug effects on the full regulatory circuity of the endogenous target gene and is expected to identify compounds that act via a wider range of pathways and thereby extending this therapeutic modality to larger set of patients independent of their age. Drugs showing signs of efficacy will be designated as lead substrate reduction compounds for further in vivo animal studies.

Start Date: March 2017

Cure Sanfilippo Foundation

501c3 non-profit
(Tax ID: 46-4322131)

P.O. Box 6901
Columbia, SC 29260