Title: New Clinical Biomarkers for GM1 Gamgliosidosis

Tega Therapeutics, Inc., La Jolla CA

Investigators

Abstract

PROJECT SUMMARY GM1 gangliosidosis is a lysosomal storage disease in which the key hydrolase enzyme, beta-galactosidase is missing, resulting in toxic accumulation of gangliosides and other glycan metabolites, principally in the central nervous system. Gangliosides are glycolipids while the glycan metabolites are derived from oligosaccharides both accumulate due to the lack of the enzyme. Identifying these diverse glycan substrates is essential for understanding the neurodegenerative progression of the disease. Research has shown that these metabolites accumulate in urine and cerebral spinal fluid (CSF) and in tissues in a mouse model. This was also observed in patients so these metabolites could potentially be used as biomarkers. To facilitate use of these metabolites as non-invasive biomarkers, levels in urine and/or CSF should correspond to the levels in tissues. Previous enzyme replacement therapy studies showed promising results in a GM1 Gangliosidosis mouse model. Administering beta-galactosidase enzyme directly to the brain reduced GM1 ganglioside levels in the brain and systemically in the liver. Here, we propose using this mouse model to confirm whether the levels of the metabolites in urine and/or CSF reflect the changes observed in tissues following therapy. With success, these metabolites would serve as clinical biomarkers that would be valuable for monitoring therapy in clinical trials and diagnosing newborn patients.