Passage Bio, Inc. (NASDAQ:PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for rare monogenic central nervous system (CNS) disorders, announced today the presentation by its collaborator University of Pennsylvania's Gene Therapy Program (GTP) of a digital poster at the 24th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). Gourav Roy Choudhury, Ph.D., a senior research investigator at GTP, will report on the development and utility of a novel Arylsulfatase A-deficient mouse model in reproducing key aspects of human metachromatic leukodystrophy (MLD) neuropathology to enable evaluation of efficacy of adeno-associated virus (AAV) gene therapy. Preliminary findings showed the administration of Passage Bio's gene therapy candidate PBML04 (AAVhu68.GTP-207) significantly reduced the neurological deficits of MLD in this model.
"This novel animal model makes it possible to evaluate the pre-clinical efficacy of our AAV-mediated gene therapy for MLD," said Bruce Goldsmith, Ph.D., President and Chief Executive Officer of Passage Bio. "One of the major challenges in developing treatments for MLD has been the limited availability of mouse models and scarcity of phenotype in existing models. This model reproduces important aspects of human leukodystrophy neuropathology, including key biomarkers. We are encouraged by the preliminary signs of efficacy we saw with PBML04 in this study."
The biomarkers used in the Arylsulfatase A-deficient mouse model were LAMP1, GFAP, and several sulfatide species (C16:0 and C18:0). Passage Bio's gene therapy candidate PBML04, which is at the IND-enabling stage of development, utilizes an AAV viral vector to deliver a codon-optimized gene sequence encoding functional ARSA enzyme.
ASGCT Presentation Details
Title: Development and Characterization of a Novel Arylsulfatase A-deficient Mouse Model of Metachromatic Leukodystrophy to Evaluate the Efficacy of Gene Therapy
Date and time: Tuesday, May 11, 2021, 8:00am – 10:00am ET
Presenter: Gourav Roy Choudhury, Ph.D., University of Pennsylvania
Abstract number: 494