AAV-GNPTAB

AAV-GNPTAB is an adeno-associated virus (AAV)-based gene replacement therapy designed to treat mucolipidosis II/III (ML II/III), a multisystem lysosomal storage disorder caused by mutations in the GNPTAB gene. The therapy delivers a functional, wild-type GNPTAB cDNA sequence to restore the activity of N-acetylglucosamine-1-phosphotransferase, an enzyme essential for the mannose-6-phosphate (M6P)-dependent trafficking of lysosomal enzymes. Developed by researchers at the University of Massachusetts Chan Medical School, the program has explored various AAV capsids (such as AAV9 and AAV-PHP.eB) and promoters (including SMN88, EF1 alpha, and the endogenous GNPTAB promoter) to optimize systemic biodistribution and central nervous system (CNS) coverage. Preclinical studies in the Nym/Nym mouse model are focused on evaluating efficacy across multiple organ systems, including the brain and bone, which are prominently affected in mucolipidosis patients.