Passage Bio Announces Publication of Preclinical Data That Show Single Injection of Optimized AAV Vector into Cerebral Spinal Fluid Corrects Neurological Disease, Supporting Advancement of PBGM01 into Clinic

The study conducted by the University of Pennsylvania’s Gene Therapy Program supports the potential of Passage Bio’s PBGM01 to correct the underlying genetic defect of GM1 gangliosidosis, a rare, life-threatening disease most common in infants

PHILADELPHIA, Oct. 13, 2020 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, today announced publication of data in a murine model of GM1 gangliosidosis (GM1) demonstrating that a single intracerebroventricular injection of an optimized adeno-associated virus (AAV) into the cerebral spinal fluid (CSF) resulted in significant expression of Beta-galactosidase (β-gal) in the brain and peripheral tissues, and demonstrated dose-related reductions in neuronal lysosomal storage lesions, neurological impairment and improvement in survival. These data were published online ahead of print in the November issue of the peer-reviewed scientific journal Human Gene Therapy (HGT).

“This study suggests that delivery of an AAV vector optimized to express b-gal directly into the CSF restored b-gal activity in the brain and, if further developed and tested in human clinical trials, may be effective in modifying and preventing the devastating effects of the genetic disease GM1,” said James Wilson, M.D., Ph.D., director of the Gene Therapy Program at the University of Pennsylvania (Penn) and chief scientific advisor of Passage Bio. “The AAV vector used in the study is the same as Passage Bio’s PBGM01 gene therapy, which is designed to deliver a functional human GLB1 gene into the brain and optimized to express β-gal. These preclinical study data support the further development of PBGM01 as a potential therapy for patients suffering from GM1.”  

GM1 is a rare and often life-threatening monogenic lysosomal storage disease caused by mutations in the GLB1 gene, which encodes lysosomal acid β-gal. Reduced β-gal activity results in the accumulation of toxic levels of GM1 in neurons throughout the brain, causing rapidly progressing neurodegeneration. GM1 manifests as a continuum of disease and is most severe in the infantile form, which is characterized by onset in the first six months of life with hypotonia (reduced muscle tone), progressive CNS dysfunction, and rapid developmental regression. Life expectancy for infants with GM1 is two to four years, and infantile GM1 represents approximately 60 percent of the incidence of 0.5 to 1 in 100,000 live births. Currently, there are no approved disease-modifying therapies available.