Phase 1/2 Trial of AXO-AAV-GM1 Gene Therapy for the Treatment of Infantile- and Juvenile-onset GM1 Gangliosidosis

GM1 gangliosidosis is a rare, fatal, neurodegenerative lysosomal storage disorder caused by variants in GLB1 encoding the lysosomal hydrolase β-galactosidase (β-gal). The resulting enzyme deficiency leads to a toxic accumulation of GM1 ganglioside, predominantly in the central nervous system (CNS) where its rate of synthesis is the highest, but also in peripheral tissues. GM1 gangliosidosis is uniformly fatal, and there are no disease-modifying treatments currently available. As this is a monogenic disorder, it is an ideal target for gene therapy to deliver β-gal to the CNS and periphery, with the potential to halt further neurodegeneration, restore function and ameliorate symptoms.