Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development

Technological advances and the desire to reduce dependence on animal models have brought human-relevant models to the forefront of drug development. This paradigm shift is leveraging the advances in <i>in vitro</i> systems and new approach methodologies (NAMs), which was the focus of a workshop convened by the Health and Environmental Sciences Institute (HESI) in May 2024. Highlights included discussions on predicting cardiac failure modes and the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), microfluidic systems like BioFlux™, and engineered heart tissues in enhancing early-stage drug safety assessments. Regulatory perspectives underscored the challenges and potential for integrating NAMs into submissions, advocating for standardized reporting and validation protocols. Case studies where NAMs offered superior predictivity compared to traditional methods are emerging and offer insights into a roadmap forward. However, there remains a need for collaboration among academia, industry, and regulatory bodies to ensure robust validation and adoption. These efforts aim to refine cardiovascular drug discovery, reduce attrition rates, and accelerate the transition toward more ethical and efficient preclinical testing paradigms.

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Publication Details

Journal
International Journal of Toxicology
Published
2025-09-09
DOI
https://doi.org/10.1177/10915818251375348
Primary Topic
Pluripotent Stem Cells Research
Type
article
Field-Weighted Citation Impact
0.00
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article

Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development

Sandy Eldridge, Alex Savtchenko, Yasunari Kanda, Xi Yang et al.
International Journal of Toxicology
Pluripotent Stem Cells Research
article

Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development

Sandy Eldridge, Alex Savtchenko, Yasunari Kanda, Xi Yang, Brian R. Berridge, Anthony Bahinski, William B. Mattes, James M. Oliphant, Joseph C. Wu, Ronald L. Wange, Chengyi Tu, Jennifer Pierson, Li Pang, Natalie E. Simpson, Khuram W. Chaudhary, Jeffrey Siegel, Todd Bourcier, Daniel Bramham
article en

Abstract

Technological advances and the desire to reduce dependence on animal models have brought human-relevant models to the forefront of drug development. This paradigm shift is leveraging the advances in <i>in vitro</i> systems and new approach methodologies (NAMs), which was the focus of a workshop convened by the Health and Environmental Sciences Institute (HESI) in May 2024. Highlights included discussions on predicting cardiac failure modes and the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), microfluidic systems like BioFlux™, and engineered heart tissues in enhancing early-stage drug safety assessments. Regulatory perspectives underscored the challenges and potential for integrating NAMs into submissions, advocating for standardized reporting and validation protocols. Case studies where NAMs offered superior predictivity compared to traditional methods are emerging and offer insights into a roadmap forward. However, there remains a need for collaboration among academia, industry, and regulatory bodies to ensure robust validation and adoption. These efforts aim to refine cardiovascular drug discovery, reduce attrition rates, and accelerate the transition toward more ethical and efficient preclinical testing paradigms.

International Journal of ToxicologyVol. 44(6)
National Center for Toxicological Research (US), United States Food and Drug Administration (US), Center for Drug Evaluation and Research (US), Bristol-Myers Squibb (Germany) (DE), RTI International (US), Teradyne (United States) (US), Cardiovascular Institute of the South (US), LabCorp (United States) (US), Bioscience Research (US), Bristol-Myers Squibb (United States) (US), National Institute of Occupational Safety and Health (JP), Frederick National Laboratory for Cancer Research (US), Clinical Solutions (US), School District of Philadelphia (US), Stanford Medicine (US), National Cancer Institute (US), Health and Environmental Sciences Institute (US), Food and Drug Administration (TH), National Institute of Health Sciences (JP), Stanford University (US)
Openalex Percentile: Top 79%
Pluripotent Stem Cells Research
DOIOpen Access PDFOpenAlex
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