In vivo validation of novel non-invasive PHP.eB AAVs as a potential therapeutic approach for alpha-synucleinopathies.

ABSTRACT: Parkinson's disease (PD) is characterized by the accumulation of alpha-synuclein (aSyn) aggregates in specific brain regions, which are likely to be the disease-causing entities. Herein, we employed novel, systemically administered, brain-penetrating viral vectors (PHP.eB AAVs) in order to evaluate the potential therapeutic utility of lowering the endogenous aSyn protein burden in the aSyn pre-formed fibril (PFF)-mouse model. Such vectors expressing short hairpin RNAs or micro RNAs targeting the mouse Snca transcript (or respective scrambled control sequences) were intravenously administered in adult wild-type mice and two weeks later human aSyn PFFs were injected into the dorsal striatum. Following the administration of the Snca-targeting PHP.eB AAVs, a successful widespread viral transdu

SUBMITTER: Fouka M 

PROVIDER: S-EPMC12482393 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature