Passage Bio (NASDAQ:PASG) announces publication of data in a murine model of GM1 gangliosidosis (GM1) demonstrating that a single intracerebroventricular injection of an optimized adeno-associated virus (PBGM01) 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.
GM1 is a rare and often life-threatening lysosomal storage disease caused by mutations in the GLB1 gene, which encodes lysosomal acid β-gal.
The mice received the single administration at age one month and were evaluated over 300 days. β-gal activity was increased significantly in the CSF and serum of the vector-treated mice compared to vehicle control-treated mice.
Considerable improvements in gait assessments and preservation of neurological function were observed throughout the study period.
There were significant decreases in lysosomal storage lesions of vector-treated animals, and by day 300, all animals that received the two highest doses were still alive, whereas none of the vehicle control-treated animals had survived.
“This study suggests that delivery of an AAV vector optimized to express β-gal directly into the CSF restored β-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., Chief Scientific Advisor of Passage Bio.
The company expects to initiate dosing of PBGM01 in a Phase 1/2 trial late in Q4 or early in Q1 2021, and remains on track to report initial 30-day safety and biomarker data late in H1 2021.