AAV-delivered PPT1 provides long-term neurological benefits in CLN1 mice and achieves therapeutic levels in sheep brain.

ABSTRACT: CLN1 disease is a fatal neurodegenerative condition caused by deficiency in palmitoyl-protein thioesterase 1 (PPT1), for which no disease-modifying therapy exists. The disease affects the entire central nervous system (CNS), necessitating widespread delivery of therapeutics to the brain and spinal cord. Adeno-associated virus (AAV)-based PPT1 gene therapy delivered intrathecally has been tested in mouse models but has shown limited efficacy due to inadequate brain bioavailability. Here, to maximize therapeutic benefit, PPT1 was engineered for improved cross-correction capabilities, packaged in Spark100, a neurotropic AAV capsid, and administered through intracerebroventricular route in neonatal Ppt1^-/- mice. This achieved sustained expression of PPT1 protein across the CNS, incl

SUBMITTER: Alam MS 

PROVIDER: S-EPMC12848131 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature