Award
National Institute of Neurological Disorders and Stroke 1U19NS138975-01
Discovery and/or Validation of Pharmacodynamic Markers
Recipient
University of North Carolina at Chapel Hill, NC, United States
Award Amount
$807,274.00
Ceiling
$807,274.00
Awarded
September 18, 2024
Identifier
1U19NS138975-01
This NIH-funded project aims to develop innovative pharmacodynamic markers for pain research, including receptor internalization assays, brain-wide activity markers, and PET imaging agents to evaluate CNS receptor occupancy.
Description
Research Component (RC) 4 focuses on developing pharmacodynamic (PD) markers indicating molecular target engagement of pain assets, such as receptor occupancy or gene transcription. The goals include developing pre-clinical PD markers to test target engagement of the NTSR1 asset generated in RC3, and creating a PD marker suitable for measuring NTSR1 occupancy in the human brain. The project involves developing an NTSR1 internalization PD assay using a novel Ntsr1Venus knockin mouse, creating an unbiased PD assay based on inhibition of c-fos transcription across the brain using mouse genetics, tissue clearing, and light-sheet microscopy, and developing a PET imaging agent by synthesizing and validating a radiolabeled SBI-553 analog to evaluate CNS NTSR1 occupancy in rodents and humans.