Saint Peter’s University Hospital Site of Global Phase I Trial

The Children’s Hospital at Saint Peter’s University Hospital has announced that it has dosed the first patient in Imagine-1, a global Phase 1/2 clinical trial program for PBGM01, an adeno-associated virus (AAV)-delivery gene therapy being developed by Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company, that is being studied for the treatment of infantile GM1 gangliosidosis (GM1), a fatal genetic condition.

Saint Peter’s was chosen as one of 10 international clinical trial sites for the global Imagine-1 study for PBGM01 by Passage Bio because of its internationally recognized geneticist with expertise in lysosomal storage diseases, Debra-Lynn Day-Salvatore, MD, PhD, FAAP, FACMG, chair of the Department of Medical Genetics and Genomic Medicine, and principal investigator for the Imagine-1 trial. Saint Peter’s is home to one of the largest comprehensive Lysosomal Disease Therapy Centers in the United States. Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. Nearly 50 of these disorders have been described to date with new lysosomal storage disorders continuing to be identified.

GM1, a rare monogenic lysosomal storage disease, is 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 toxic levels of GM1 gangliosides in neurons throughout the brain, causing rapidly progressive neurodegeneration. Accumulation also results in progressive damage to other tissues including the heart, liver, and bones and manifests with hypotonia (reduced muscle tone), progressive CNS dysfunction, seizures, and rapid developmental regression. Life expectancy for infants with GM1 ranges from 2-10 years, and infantile GM1 represents approximately 60 percent of the global GM1 incidence of 0.5 to 1 in 100,000 live births.

Imagine-1 is a global study of PBGM01 administered by a single injection directly into the cisterna magna, an opening in the subarachnoid space surrounding the brain, in pediatric subjects with early and late infantile GM1. PBGM01 delivers a functional GLB1 gene encoding the β-gal enzyme to the brain and peripheral tissues that in preclinical studies showed reduced accumulation of GM1 gangliosides. By reducing the accumulation of GM1 gangliosides, PBGM01 has the potential to reverse neuronal toxicity, thereby restoring developmental potential. In preclinical models, PBGM01 has demonstrated broad brain distribution and high levels of expression of the β-gal enzyme in both the CNS and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1. PBGM01 is now being tested in patients with infantile GM1 gangliosidosis to determine whether such treatment is safe and effective by showing specified improvements in neurological function, developmental potential, overall survival, and the quality of life for patients with GM1.

Dr. Day-Salvatore has attracted a multidisciplinary team of physicians and medical experts that work collaboratively to offer world-class medical care that delivers hope to parents when they have nowhere else to turn. The genetics research team at Saint Peter’s is anchored by Daniela Silva, MSN, RN, CCRN, CCRP, clinical research nurse coordinator, and, apart from other members of the Genetics Department, includes representatives from the following disciplines: Pediatric Neurology, Interventional Radiology, Neurodevelopmental Pediatrics/ Child Psychology, Pediatric Ophthalmology, Pediatric Audiology, Pediatric Anesthesiology, Pediatric Cardiology, Pharmacy, Radiology, Laboratory Medicine, Pediatric Intensive Care, Nursing staff across all disciplines, Respiratory Therapy, Child Life, Pastoral Care, and Multimedia.