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Safety concerns associated with BACE1 inhibitors - past, present, and future
Aniketh Naidu1, Bret Silverglate1, Mary Silverglate2
1Department of Psychiatry and Behavioral Neuroscience, Division of Geriatrics, Saint Louis University School of Medicine, St. Louis, MO, USA.
Introduction:
BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) inhibitors have shown promise in treating Alzheimer's disease (AD) by reducing amyloid-beta (Aβ) production. However, clinical trials of inhibitors such as atabecestat, verubecestat, and lanabecestat have faced challenges, including limited efficacy and significant adverse effects.
Areas Covered:
This narrative review discusses randomized-controlled trials of BACE1 inhibitors. Literature searches were conducted using PubMed and Web of Science for studies from 2010 to 2024. Association with BACE1's widespread expression beyond the brain shows adverse effects such as anxiety, depressive symptoms, and hepatotoxicity.
Expert Opinion:
The trial results underscore the need for CNS-specific BACE1 inhibitors to reduce adverse effects. Future research should focus on optimizing drug design and identifying additional therapeutic avenues, such as prostate cancer and insulin resistance.
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