Award
National Institute of Neurological Disorders and Stroke 5R01NS126279-04
Network modulation to improve gene therapy in CLN3 disease
Recipient
Children's Hospital of Philadelphia, Philadelphia, PA, United States
Award Amount
$487,607.00
Ceiling
$487,607.00
Awarded
July 27, 2026
Identifier
5R01NS126279-04
This award funds research to understand and improve gene therapy efficacy in CLN3 disease by studying early network changes and exploring network modulation.
Description
In two-thirds of lysosomal storage disorders (LSD), patients suffer neurologic symptoms that are not corrected by most therapies, including gene replacement, especially if treatment is given after symptom onset. We recently identified pathologic changes in hippocampal network dynamics that arise early in CLN3 disease, a representative LSD, and the most common cause of pediatric dementia. The goal of this project is to understand if early, progressive changes in network physiology in CLN3 disease will establish a point beyond which gene therapy cannot restore function to a diseased neuronal circuit and to explore if modulating network activity can modify the efficacy of gene replacement.