[Current challenges and future perspectives of iPSC-based neurotoxicity testing]

Area of Science:

• Neuroscience
• Toxicology
• Biotechnology

Background:

• Predicting drug-induced central nervous system (CNS) side effects is vital for drug development and safety.
• Current animal-based evaluation systems show limited predictivity in humans and are resource-intensive.
• There is a growing need for reliable, efficient in vitro alternatives for CNS safety assessment.

Purpose of the Study:

• To review current trends in central nervous system safety assessment methods.
• To explore the application of New Approach Methodologies (NAMs) in neurotoxicity evaluation.
• To highlight the potential of human induced pluripotent stem (iPS) cells and in silico approaches.

Main Methods:

• Review of existing literature and international trends in neurotoxicity assessment.
• Exploration of in vitro methods, including human iPS cell technology.
• Discussion of in silico modeling for developmental neurotoxicity assessment.

Main Results:

• Human iPS cell technology is successfully applied for cardiotoxicity assessment and shows promise for neurotoxicity.
• In silico and human iPS cell-based approaches are increasingly promoted for developmental neurotoxicity.
• International bodies like the OECD are preparing guidance for developmental neurotoxicity assessment.

Conclusions:

• New Approach Methodologies (NAMs), particularly those utilizing human iPS cells and in silico tools, represent a significant advancement in CNS safety evaluation.
• These methods offer a more predictive, ethical, and cost-effective alternative to traditional animal testing.
• The ongoing development of international guidelines will further facilitate the adoption of these novel assessment strategies.