Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles.

Drug repurposing can accelerate drug development while reducing the cost and risk of toxicity typically associated with de novo drug design. Several disorders lacking pharmacological solutions and exhibiting poor results in clinical trials - such as Alzheimer's disease (AD) - could benefit from a cost-effective approach to finding new therapeutics. We previously developed a neural network model, Z-LaP Tracker, capable of quantifying behaviors in zebrafish larvae relevant to cognitive function, including activity, reactivity, swimming patterns, and optomotor response in the presence of visual and acoustic stimuli. Using this model, we performed a high-throughput screening of FDA-approved drugs to identify compounds that affect zebrafish larval behavior in a manner consistent with the distinct behavior induced by calcineurin inhibitors. Cyclosporine (CsA) and other calcineurin inhibitors have garnered interest for their potential role in the prevention of AD. We generated behavioral profiles suitable for cluster analysis, through which we identified 64 candidate therapeutics for neurodegenerative disorders.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Brown University submitted a patent application for the treatment of neurodegenerative disease using CsA-type compounds (application 63/193,935, Robbert Creton - inventor, Sara Tucker Edmister, Rahma Ibrahim, Rohit Kakodkar and Jill A. Kreiling - contributors). The authors declare that they do not have other competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)