Enhancer-based AAV approach for selective AADC delivery reduces motor symptoms and dyskinesia in Parkinson's mouse models.

Enhancer-driven AAVs with BBB-penetrant capsids drive cell type-specific AADC expression in PD mouse models, improving survival and reducing motor deficits and L-DOPA-induced dyskinesia.

• Why it matters: L-DOPA helps Parkinson’s disease symptoms but long-term use can lead to L-DOPA-induced dyskinesia, and AAV AADC delivery is often invasive.
• What they did: The study engineered enhancer-driven AAVs to express AADC in key striatal cell types and tested them with L-DOPA across two delivery routes and PD mouse models, comparing against ubiquitous AADC expression.
• The result: Cell type-specific AADC expression produced similar or greater phenotypic rescue than ubiquitous AADC, and enhancer-driven specificity was conserved in non-human primates, supporting a less invasive, better tolerated strategy.

AI summary of the abstract · may contain errors · not medical advice · read the paper.