AAV9-GLB1 gene therapy

AAV9-GLB1 gene therapy refers to a class of investigational genetic treatments designed to address GM1 gangliosidosis, a severe lysosomal storage disorder caused by biallelic mutations in the GLB1 gene. The therapy utilizes an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the human GLB1 gene, which encodes the enzyme β-galactosidase. Deficiency of this enzyme leads to the toxic accumulation of GM1 gangliosides, particularly in the central nervous system (CNS), resulting in progressive neurodegeneration. The AAV9 vector is selected for its ability to cross the blood-brain barrier and achieve widespread distribution in the CNS following intravenous administration. Notable programs include AXO-AAV-GM1, originally developed by the National Human Genome Research Institute (NHGRI) and licensed to Sio Gene Therapies (formerly Axovant), and TSHA-101, developed by Taysha Gene Therapies. Clinical trials, such as NCT03952637, have evaluated the safety and efficacy of this approach in infantile and juvenile populations, demonstrating increases in CSF β-galactosidase activity and reductions in GM1 ganglioside concentrations.