A 31P MRS study of Target Engagement of Terazosin in Neurodegenerative Diseases
Jia Xu1, Sarah E Ernst2, Erin E Reasoner3, Stephen A Cross3, Alivia N Brinker3, Cameron A Keomanivong4, Zach Elias4, Daniel R. Thedens1, Nandakumar Narayanan4, Jordan L Schultz3, Michael J Welsh2, and Vincent A Magnotta1
1Radiology, University of Iowa, Iowa City, IA, United States, 2Internal Medicine, University of Iowa, Iowa City, IA, United States, 3Psychiatry, University of Iowa, Iowa City, IA, United States, 4Neurology, University of Iowa, Iowa City, IA, United States
Terazosin is an FDA-approved medicine that has been used primarily for men and data for women are missing. For the first time, the target engagement of Terazosin in neurodegenerative diseases was assessed for both sexes. We chose the βATP/Pi ratio as a biomarker to study the brain energy metabolism and found strong correlations between the in vivo brain ATP levels to whole blood ATP levels. We observed clear sex differences in response to different TZ doses in both mice and humans. Our data suggest that the optimal dose for females may need to be lower as compared to males.
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