Dataset Information

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

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.

SUBMITTER: Schultz JL

PROVIDER: S-EPMC8862665 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Schultz Jordan L JL Brinker Alivia N AN Xu Jia J Ernst Sarah E SE Tayyari Fariba F Rauckhorst Adam J AJ Liu Lei L Uc Ergun Y EY Taylor Eric B EB Simmering Jacob E JE Magnotta Vincent A VA Welsh Michael J MJ Narayanan Nandakumar S NS

Parkinsonism & related disorders 20211127

<h4>Background</h4>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.<h4>Methods</h4>We performed a 12-week pilot study in people with PD. Participants were randomized to receive 5 mg TZ or ...[more]

PMID: 34894470

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Project description:BackgroundGait disorder, a key contributor to fall and poor quality of life, represents a major therapeutic challenge in Parkinson's disease (PD). The efficacy of acupuncture for PD remains unclear, largely due to methodological flaws and lack of studies using objective outcome measures.ObjectiveTo objectively assess the efficacy of electroacupuncture (EA) for gait disorders using body-worn sensor technology in patients with PD.MethodsIn this randomized pilot study, both the patients and assessors were masked. Fifteen PD patients were randomly assigned to an experimental group (n = 10) or to a control group (n = 5). Outcomes were assessed at baseline and after completion of three weekly EA treatments. Measurements included gait analysis during single-task habitual walking (STHW), dual-task habitual walking (DTHW), single-task fast walking (STFW), dual-task fast walking (DTFW). In addition, Unified Parkinson's Disease Rating Scale (UPDRS), SF-12 health survey, short Falls Efficacy Scale-International (FES-I), and visual analog scale (VAS) for pain were utilized.ResultsAll gait parameters were improved in the experimental group in response to EA treatment. After adjustment by age and BMI, the improvement achieved statistical significant level for gait speed under STHW, STFW, and DTFW (9%-19%, p<0.05) as well as stride length during DTFW (9%, p = 0.037) and midswing speed during STFW (6%, p = 0.033). No significant changes were observed in the control group (p>0.110). The highest correlation between gait parameters and UPRDS scores at baseline was observed between gait speed during STFW and UPDRS II (r = -0.888, p = 0.004). The change in this gait parameter in response to active intervention was positively correlated with baseline UPDRS (r = 0.595, p = 0.057). Finally, comparison of responses to treatment between groups showed significant improvement, prominently in gait speed (effect size 0.32-1.16, p = 0.001).ConclusionsThis study provides the objective proof of concept for potential benefits of non-pharmaceutical based EA therapy on enhancing gait in patients with PD.Trial registrationClinicalTrials.gov NCT02556164.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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