Mark Forman, MD, PhD, Chief Medical Officer at Passage Bio, discusses the mechanism of action of PBGM01, an investigational gene therapy for infantile GM1 gangliosidosis.

GM1 gangliosidosis is an inherited lysosomal storage disorder caused by mutations in the GLB1 gene, which encodes the lysosomal enzyme beta-galactosidase (β-gal). Reduced β-gal activity results in the accumulation of GM1 gangliosides in neurons, causing rapidly progressive neurodegeneration. Progressive damage is also seen in the heart, liver, and bones. The condition may be classified into three major types: classic infantile (type 1); juvenile (type 2); and adult onset or chronic (type 3). Currently, there is no targeted treatment approved for GM1 gangliosidosis so management is primarily supportive.

As Dr. Forman explains, PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1, the most aggressive form of this disease. PBGM01 utilizes a next-generation AAVhu68 capsid to deliver a functional GLB1 gene encoding beta-galactosidase to the brain and peripheral tissues. By increasing beta-galactosidase activity, PBGM01 has the potential to reduce accumulation of toxic GM1 gangliosides and reverse neuronal toxicity, thereby restoring developmental potential. 

To learn more about GM1 gangliosidosis and other rare lysosomal storage disorders, visit