WORLDSymposium™ 2023 poster presentation: An engineered β-galactosidase for the potential treatment of GM1 Gangliosidosis via AAV gene therapy
GM1 Gangliosidosis is a rare neurodegenerative lysosomal storage disorder that results in neuronal and peripheral tissue pathology with progressive neurodegeneration. Gene therapy delivering GLB1 to the central nervous system (CNS) offers potential to slow and reverse disease progression, but intrinsic limitations of the human β-gal enzyme may limit the effectiveness of this approach. We applied the CodeEvolver® protein engineering platform to identify improved GLB1 variants for delivery as a transgene. We evaluated the performance of the lead variant via administration as a gene therapy using a GM1 mouse model with deficient β-gal activity. Results are presented in this poster and show the promise of an optimized GLB1 transgene as a next-generation gene therapy that could drastically improve the quality of life for patients.