NIH Reporter #5R01NS126279-04

Network modulation to improve gene therapy in CLN3 disease

The award supports research on improving gene therapy for CLN3 disease by studying network physiology changes and testing circuit modulation in mouse models to enhance therapy efficacy.

Description

This project aims to understand the early, progressive changes in network physiology in CLN3 disease, a lysosomal storage disorder (LSD) and the most common cause of pediatric dementia. The research investigates whether there is a therapeutic window during which gene therapy can restore neuronal circuit function and explores if modulating network activity can enhance gene therapy efficacy. The study involves electrophysiological assessments of hippocampal network dynamics in mouse models, focusing on the dentate gyrus and entorhinal cortex. It hypothesizes that early developmental abnormalities in neuronal circuits limit the effectiveness of gene replacement therapy and seeks to define this window and test circuit modulation strategies.

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