Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology

Area of Science:

• Pharmacology
• Systems Biology
• Drug Development

Background:

• Traditional target-centric pharmacology faces low success rates in drug development.
• Existing animal models show limited concordance with human disease and ADME-Tox.
• New technologies are needed to improve the efficiency and accuracy of drug discovery.

Purpose of the Study:

• Introduce Quantitative Systems Pharmacology (QSP) as a novel approach to drug discovery.
• Present human Microphysiology Systems (MPS) as advanced experimental models.
• Highlight the potential of integrating QSP and MPS for enhanced drug development.

Main Methods:

• QSP utilizes computational, systems biology, and multiscale experimental methods.
• MPS are based on human cells (primary, stem, iPSCs) to mimic human tissue and organ functions.
• Both QSP and MPS incorporate models for ADME-Tox (Absorption, Distribution, Metabolism, Excretion, Toxicity) and disease.

Main Results:

• QSP offers a complementary approach to traditional pharmacology.
• MPS provide improved human-relevant models compared to animal studies.
• The integration of QSP and MPS demonstrates significant potential for advancing drug discovery.

Conclusions:

• QSP and MPS represent a new paradigm in pharmacology and drug development.
• Combining QSP with MPS can enhance the prediction of therapeutic efficacy and safety.
• This integrated approach addresses key limitations in the current drug discovery and development pipeline.