Gene Therapy Safely Delivers Functional Beta-Galactosidase Enzyme Activity to Children with Gangliosidosis 1
In the Imagine-1 phase 1/2 open-label, dose-escalation study (NCT04713475) of gene therapy (PBGM01; Passage Bio, Philadelphia PA) increased functional β-galactosidase activity in children with gangliosidosis type 1 (GM1). Loss of β-galactosidase function causes GM1, and the gene therapy replaced this function in both serum and cerebrospinal fluid of 2 treated children.
In the first child, enzyme activity at 30 days was 1.5 that of baseline and this increase was maintained at 6 months. For the second child treated, enzyme activity at 30 days was 4.8 times that of baseline. No serious adverse events occurred. All moderate adverse events resolved without treatment and were considered unrelated to the gene therapy.
The Independent Data Monitoring Committee (IDMC) has recommended proceeding to additional planned cohorts of participants with early and late infantile GM1. Participant recruitment has begun for a high-dose cohort (Cohort 2) of patients with late infantile GM1 and a low-dose cohort (Cohort 3) of patients with early infantile GM1.
“Children with infantile GM1 experience a rapid decline in neurologic function and unfortunately, there are no disease-modifying treatments available to them,” said Roberto Giugliani, MD, PhD, Department of Genetics, Federal University of Rio Grande do Sul. “The disease is devastating to patients and their families, so I am encouraged by the early data with PBGM01—that it was not only well-tolerated but also showed an increase in activity of the β-galactosidase enzyme in both serum and CSF. I look forward to the continued clinical advancement of PBGM01 and learning its potential for GM1 patients.”
Of note, the gene therapy being evaluated is a novel adeno-associated viral vector-based gene therapy, which uses a next-generation AAVhu68 capsid. Treatment is administered through the cisterna magna to deliver functional β-galactosidase DNA to the brain and peripheral tissues.