Gene therapies from Passage Bio, Locanabio; Lava’s antitumor bispecific, health disparities in Alzheimer’s and more

Passage Bio’s frontotemporal dementia gene therapy
University of Pennsylvania spinout Passage Bio Inc. reported that administration of PBFT02, an AAV1-GRN vector, led to elevated levels of PGRN in the brain and cerebral spinal fluid (CSF), reduced lysosomal storage lesions, normalized lysosomal enzyme activity and corrected microgliosis in mouse models of frontotemporal dementia caused by GRN mutations. Intra-cisterna magna injection of PBFT02 in rhesus macaques led to PGRN expression levels up to 40-fold normal human levels in CSF. Based on the data, published in Annals of Clinical and Translational Neurology, Passage plans to initiate a Phase I/II trial of PBFT02 in 1H21 (see “Passage Bio Outlines Clinical Goals”).

Locanabio’s RNA-targeting gene therapy
Scientists at Locanabio Inc, with collaborators at University of California San Diego and University of Florida, showed in Nature Biomedical Engineering that one dose of its AAV vector encoding a nuclease-dead Cas9 and guide RNA targeting CUG repeats eliminated toxic RNA with microsatellite repeat expansions in the DMPK gene that causes myotonic dystrophy type 1. DM1 mice treated with the therapy sustained expression of the Cas9 for up to three months and showed improved muscle health...