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CLINICAL TRIAL article
Front. Neurosci.
Sec. Neuropharmacology
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1516746
Exploratory Analysis of Bezisterim Treatment Associated With Decreased Biological Age Acceleration, and Improved Clinical Measure and Biomarker Changes in Mild-to-Moderate Probable Alzheimer's Disease
Provisionally accepted
Chris Reading 1*
Jiayan Yan 1
Marcia Testa 2 Donald Simonson 2 Hira Javaid 3 Lisa Schmunk 3
Daniel Martin-Herranz 3 Robert Brooke 4 Juozas Gordevicius 4
Jeffrey Yangang Zhang 5 Harvey Yuan 5 Clarence Ahlem 1 Lixia Wang 1 Penelope Markham 1 Nily Osman 1 Stephen O'Quinn 1 Joseph Palumbo 1- 1 BioVie Pharma, Carson City, United States
- 2 Phase V Technologies, Wellesley Hills, Massachusetts, United States
- 3 Chronomics, London, United Kingdom
- 4 Clock Foundation, Torrance, California, United States
- 5 Princeton Pharmatech, Princeton, New Jersey, United States
Aging is the greatest risk factor for sporadic Alzheimer’s disease. Chronic low-grade inflammation associated with aging drives cognitive impairment through multiple mechanisms involving oxidative stress, insulin resistance, and dysregulation of metabolic, immunologic, and hematologic systems. In a 7-month, randomized, double-blind, placebo-controlled trial (NCT04669028), we investigated the safety and activity of bezisterim, a first-in-class, oral, blood-brain barrier–permeable, anti-inflammatory agent on cognitive, molecular, biochemical, physiological, and biological aging parameters in a subset of 50 mild-to-moderate probable Alzheimer’s disease participants, with source-document verified clinical measures and available samples, that completed the protocol. This report focuses on epigenetic, metabolic, biomarker, and cognitive measures in the exploratory biomarker population that completed the protocol. Bezisterim was associated with directional (nonsignificant) improvements in multiple measures of cognitive and functional performance compared to placebo, with correlations to biological age (determined by DNA methylation “clocks”) and to metabolism, inflammation, and dementia biomarkers. In addition, clinical measures correlated with the extent of DNA methylation of certain cytosine-phosphate-guanine (CpG) sites in genes associated with metabolic inflammation and neurodegeneration. The results suggest the possible use of bezisterim to target multifactorial processes underlying dementia.
Keywords: Alzheimer's, Neuroinflammation, Insulin, Methylation, NE3107, bezisterim, Cognition, Dementia
Received: 24 Oct 2024; Accepted: 01 Apr 2025.
Copyright: © 2025 Reading, Yan, Testa, Simonson, Javaid, Schmunk, Martin-Herranz, Brooke, Gordevicius, Zhang, Yuan, Ahlem, Wang, Markham, Osman, O'Quinn and Palumbo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chris Reading, BioVie Pharma, Carson City, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.