Pluripotent stem cells for neurodegenerative disease modeling: an expert view on their value to drug discovery

ABSTRACT

Introduction

Neurodegenerative diseases have become a major global health concern, posing a huge disease burden on patients and their families. Although there has been rapid progress in the development of therapies, a lack of accurate disease models and efficient drug screening platforms have made achieving a breakthrough difficult. The technology of human-induced pluripotent stem cells (iPSCs) shows better recapitulation of disease pathophysiology and provides a more accessible supply of patient-specific samples compared to other modeling methods. It has been a powerful tool for mechanism exploration and drug development.

Areas covered

This review describes the recent use of human iPSC-derived cells for modeling neurodegenerative disorders and discovering potential drugs.

Expert opinion

Model systems based on iPSC-derived cells have created a paradigm shift in drug discovery. Accuracy, consistency, translatability, and cost-effectiveness are the four major focuses of academic and industrial communities to fulfill the potential of iPSC technology for their purposes. It is the art of balance between these four factors to generate efficacious outputs with maximum efficiency. Future studies should persist in refining this technology and promote its application in this field to benefit all the disease-affected population eventually.

KEYWORDS:

• Human iPS cells
• neurodegenerative disease
• disease modeling
• drug discovery
• neuronal subtypes
• glial cell
• organoid
• screening platforms

Article highlights

• Human-induced pluripotent stem cells (iPSCs) can better recapitulate the disease-relevant pathogenesis of neurodegenerative diseases with a more accessible supply over other modeling methods, and further promote the development of new treatments.

• Various types of neural cells and three-dimensional neural structures can be more efficiently generated by the patient-derived iPSCs with improved protocols.

• Extensive application of iPSC-derived neural two-dimensional and three-dimensional structures for neurodegenerative disease modeling has been successively achieved.

• Disease models based on the iPSC-derived cell system can provide platforms for both focused screen and high-throughput screen in the early stage of drug development.

• Challenges and limitations remain in this rapidly progressive field, and future studies should focus on accuracy, consistency, translatability, and cost-effectiveness during disease modeling to fulfill the potential of iPSC technology.

This box summarizes key points contained in the article.

Acknowledgments

The authors give special thanks to Kevin Kuo for his advice during the preparation of this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.