Biomarkers

Area of Science:

• Neuroscience
• Translational Medicine
• Drug Discovery

Background:

• Neurodegenerative diseases like Alzheimer's and Parkinson's are complex, poorly understood, and pose a significant global health and economic burden.
• Current central nervous system (CNS) drug development faces high clinical trial failure rates (92%) due to issues like non-human-relevant measures and poor reproducibility.
• There is a critical need for improved pre-clinical approaches to enhance the predictive validity of drug candidates for neurodegenerative disorders.

Purpose of the Study:

• To introduce the TRanslational Initiative to DE-risk NeuroTherapeutics (TRIDENT) platform, designed to address critical gaps in neurodegenerative disease pre-clinical evaluation.
• To improve the predictive validity of pre-clinical to clinical outcomes in drug discovery for neurodegenerative conditions.
• To foster inclusivity, collaboration, and reproducibility in pre-clinical research through open science principles.

Main Methods:

• TRIDENT integrates human-induced pluripotent stem cells (iPSCs) and organoids, humanized mouse models, and marmoset models into a unified platform.
• The platform utilizes human-relevant, touchscreen-based cognitive tasks in mice and marmosets, which are highly translatable to human cognition.
• TRIDENT incorporates Sex-Based Analysis (SBA)+ and open science principles, with multi-site validation at McGill University, University of Toronto, and CAMH.

Main Results:

• The TRIDENT platform offers a novel solution for developing effective neurodegenerative disease therapies.
• It maximizes predictive validity, thereby de-risking the drug discovery and development process.
• Current evaluations focus on compounds for alpha-synucleinopathies and Alzheimer's Disease to validate the platform's efficacy.

Conclusions:

• TRIDENT is poised to revolutionize pre-clinical testing methodologies for neurodegenerative disorders.
• The platform aims to make the drug discovery process more attractive to pharmaceutical and biotechnology industries.
• This initiative is expected to accelerate the identification of effective cures and therapies for debilitating neurodegenerative conditions.