Children’s Hospital at Saint Peter’s is one of 10 selected to run global gene trial

Nationally recognized Lysosomal Disease Therapy Center at Saint Peter’s doses 1st patient suffering from Infantile GM1 Gangliosidosis in Imagine-1 study

The Children’s Hospital at Saint Peter’s University Hospital is one of 10 international clinical trial sites selected to participate in phase 1 of the global Imagine-1 study for PBGM01 by Passage Bio, a gene therapy trial for a fatal genetic condition.

Dr. Debra-Lynn Day-Salvatore, chair of the Department of Medical Genetics and Genomic Medicine and an internationally recognized geneticist with expertise in lysosomal storage diseases, will serve as the principal investigator for the Imagine-1 trial.

Saint Peter’s is home to one of the largest comprehensive Lysosomal Disease Therapy Centers in the U.S. 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.

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, clinical research nurse coordinator.

Dr. Sudipta Roychowdhury, subinvestigator on the Imagine-1 trial, is a diagnostic and interventional neuroradiologist who successfully performed the delicate injection procedure. Dr. Carlos Lastra, director of the Division of Pediatric Neurology and lead neurologist on the Imagine-1 study, is also a subinvestigator.

The group announced it has dosed the first patient.

“This clinical study requires exquisite coordination,” Day-Salvatore said. “Everyone plays a pivotal role, and I am extremely proud of the teamwork, precision and seamless workflow that resulted in the successful dosing of the first patient in the clinical trial program for PBGM01.

“I am also grateful to the patient’s family for entrusting us with the care of their precious child. We are pleased to celebrate this milestone with the patients, families and researchers that helped to bring this effort to fruition and share their hope, dreams and resolve for the future.”

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% 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.