A pilot to assess target engagement of terazosin in Parkinson's disease

Jordan L Schultz; Alivia N Brinker; Jia Xu; Sarah E Ernst; Fariba Tayyari; Lei Liu; Ergun Y Uc; Eric B Taylor; Jacob E Simmering; Vincent A Magnotta; Michael J Welsh; Nandakumar S Narayanan

doi:10.1016/j.parkreldis.2021.11.022

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A pilot to assess target engagement of terazosin in Parkinson's disease

Journal article

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A pilot to assess target engagement of terazosin in Parkinson's disease

Jordan L Schultz, Alivia N Brinker, Jia Xu, Sarah E Ernst, Fariba Tayyari, Lei Liu, Ergun Y Uc, Eric B Taylor, Jacob E Simmering, Vincent A Magnotta, …

Parkinsonism & related disorders, Vol.94, pp.79-83

11/2021

DOI: 10.1016/j.parkreldis.2021.11.022

PMCID: PMC8862665

PMID: 34894470

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https://www.ncbi.nlm.nih.gov/pmc/articles/8862665View

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Abstract

Background Impaired brain energy metabolism is a key feature of Parkinson's disease (PD). Terazosin (TZ) binds phosphoglycerate kinase 1 and stimulates its activity, which enhances glycolysis and increases ATP levels. Preclinical and epidemiologic data suggest that TZ may be neuroprotective in PD. We aimed to assess target engagement and safety of TZ in people with PD. Methods We performed a 12-week pilot study in people with PD. Participants were randomized to receive 5 mg TZ or placebo. Participants and study personnel were blinded. We assessed TZ target engagement by measuring brain ATP with 31P-magnetic resonance spectroscopy (MRS) and whole blood ATP with a luminescence assay. Robust linear regression models compared changes between groups controlling for baseline brain and blood ATP levels, respectively. We also assessed clinical measures of PD and adverse events. Results Thirteen participants were randomized. Mild dizziness/lightheadedness was more common in the TZ group, and three participants taking TZ dropped out because of dizziness and/or orthostatic hypotension. Compared to the placebo group, the TZ group had a significant increase in the ratio of βATP to inorganic phosphate in the brain. The TZ group also had a significant increase in blood ATP levels compared to the placebo group (p < 0.01). Conclusions This pilot study suggests that TZ may engage its target and change ATP levels in the brain and blood of people with PD. Further studies may be warranted to test the disease-modifying potential of TZ.

Details

Title: Subtitle: A pilot to assess target engagement of terazosin in Parkinson's disease
Creators: Jordan L Schultz
Alivia N Brinker
Jia Xu
Sarah E Ernst
Fariba Tayyari
Lei Liu
Ergun Y Uc
Eric B Taylor
Jacob E Simmering
Vincent A Magnotta
Michael J Welsh
Nandakumar S Narayanan
Resource Type: Journal article
Publication Details: Parkinsonism & related disorders, Vol.94, pp.79-83
DOI: 10.1016/j.parkreldis.2021.11.022
PMID: 34894470
PMCID: PMC8862665
NLM abbreviation: Parkinsonism Relat Disord
ISSN: 1353-8020
eISSN: 1873-5126
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: 5UL1TR002537-04, S10RR028821
Language: English
Date published: 11/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; Health Management and Policy; Iowa Neuroscience Institute; Pharmacy Practice and Science; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984199816802771

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