Advancement in early diagnosis and therapeutic intervention for Mucopolysaccharidoses

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Mucopolysaccharidoses (MPS) is a disorder that prevents the breakdown of glycosaminoglycans (GAGs), leading to their accumulation. This condition causes progressive developmental problems after birth that results in premature death. Collectively MPS is observed in about 1 in 30,000 births. There is currently no cure and the efficacy of existing treatments is impaired by delayed diagnosis and insensitive monitoring. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) together with multivariate analysis (MVA) has recently been used to analyse GAGs, demonstrating orders of magnitude greater sensitivity than existing methods. In this project, ToF-SIMS will be investigated for its ability to enable early diagnosis of MPS by analysing patient urine and blood samples and as a tool to aid in the development of new MPS therapies.GAG biosynthetic enzymes have recently been identified as potential MPS therapeutics. The interaction of these poorly understood complexes will be investigated utilising new tools that enable incorporation of affinity and fluorescent labels onto targeted enzymes using CRISPR-Cas9 gene editing. By investigating the complexes that control GAG structure and function we will identify novel therapeutic targets. The GAG profile of the cells will be analysed by ToF-SIMS and compared to the GAG profiles measured in patient samples.