Mark Forman, MD, PhD, Chief Medical Officer at Passage Bio, discusses  long-term clinical and biomarker data from Cohort 1 in the phase 1/2 Imagine-1 study of PBGM01, a gene therapy under investigation for GM1 gangliosidosis. This data was presented at the 2022 American Society of Gene and Cell Therapy annual meeting (ASGCT 2022).

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). Common signs and symptoms among all three subtypes include hypotonia, progressive CNS dysfunction, seizures, and rapid developmental regression. Currently, there is no targeted treatment approved for GM1 gangliosidosis so management is primarily supportive.

As Dr. Forman explains, the primary goal of the Imagine-1 study is to first assess safety and tolerability and then efficacy of PBGM01 in patients. Cohort 1 of the study includes two patients with late infantile GM1 administered a low dose of PBGM01. 

The interim data presented at ASGCT 2022 demonstrated that low dose PBGM01 was well-tolerated and had a favorable safety profile with patient 1 through 13 months and patient 2 through 7 months. Both patients showed continued improvement across developmental areas on the Vineland-II (caregiver-assessed) and Bayley-III (investigator-assessed) scales. Following PBGM01 administration, improvement from baseline was observed and documented across all developmental areas for patient 1, with notable progression in motor and language domains. Improvement across multiple developmental domains was also observed and documented for patient 2, despite this patient having severe developmental delay at baseline and a prior history of regression. Finally, volumetric MRI data showed meaningful growth in brain volume for patient 1, who was 15 months of age at gene transfer. Volumetric MRI showed increases in brain volume at 12 months compared to baseline for patient 1 in multiple brain regions. Patient 2, who had severe developmental delay at baseline and was 31 months of age at gene transfer, showed a slight decline in brain volume from baseline at 6 months.

To learn more about GM1 gangliosidosis and other rare lysosomal storage disorders, visit checkrare.com/diseases/lysosomal-storage-disorders/