Bridging the validation gap: organoids as functional decision systems in drug repurposing

Area of Science:

• Biotechnology
• Computational Biology
• Drug Discovery

Background:

• Drug repurposing accelerates therapeutic development but faces challenges in validating computationally identified candidates.
• A lack of human-relevant intermediate validation systems hinders the translation of potential drugs into clinical evidence.

Purpose of the Study:

• To propose human organoid platforms, enhanced by AI, as a functional decision layer in drug repurposing pipelines.
• To outline a hybrid framework integrating in silico discovery, organoid validation, and AI-driven interpretation for drug repurposing.

Main Methods:

• Coupling in silico drug candidate discovery with organoid-based functional validation.
• Integrating AI for upstream candidate prioritization and downstream response interpretation.
• Developing context-specific, fit-for-purpose functional decision layers within repurposing workflows.

Main Results:

• Organoid platforms, when combined with AI, can serve as decision-grade validation systems for drug repurposing.
• The proposed hybrid framework offers a pathway to generate biologically grounded, clinically actionable evidence.
• Identified disease categories where this approach is most applicable.

Conclusions:

• Human organoid platforms integrated with AI represent a significant advancement for drug repurposing validation.
• This approach addresses the critical evidentiary gap, facilitating the clinical translation of repurposed drugs.
• The framework aligns with evolving regulatory acceptance of New Approach Methodologies (NAMs).