Award
National Institute of Neurological Disorders and Stroke 5R37NS054154-17
The Genetics of the Neuromuscular Junction: Mechanisms and Disease Models
Recipient
Jackson Laboratory, Bar Harbor, ME, United States
Award Amount
$1,032,326.00
Ceiling
$1,032,326.00
Awarded
June 19, 2026
Identifier
5R37NS054154-17
Research project funded by NINDS to study genetic mechanisms of Charcot-Marie-Tooth disease focusing on tRNA synthetase mutations, their cellular effects, and potential treatments including pharmacological and gene therapy strategies.
Description
This project examines dominant mutations in tRNA synthetase genes that cause inherited peripheral neuropathy. The research aims to understand the biochemical and cellular basis for these diseases, test mechanisms explaining their specificity for motor and sensory neurons, and evaluate possible pharmacological and gene therapy-based treatments. The study focuses on Charcot-Marie-Tooth disease (CMT), associated with mutations in tRNA synthetase genes, and investigates the role of the integrated stress response (ISR) and ribosome stalling in disease pathology. The project includes developing cell-based models, testing disease specificity mechanisms, and evaluating pharmacological inhibition of ISR and gene therapy approaches.