New approach methodologies in neurotherapeutics development
4 affiliations
- 1Division of Translational Research, National Institute of Neurological Disorders and Stroke, NIH, 6001 Executive Blvd., Rockville, MD, 20852, USA; Corresponding author.
- 2Szczepan Baran, Chief Scientific Officer, Instem, 800 Boylston Street, Suite 1450, Boston, MA, 02199, USA
- 3Doerenkamp-Zbinden Professor and Chair for Evidence-based Toxicology, Johns Hopkins University, Baltimore, MD, 21205, USA
- 4Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
Abstract
New Approach Methodologies (NAMs) offer substantial opportunities to transform neurotherapeutics discovery, optimization, and development, reducing the timeline to translate central nervous system (CNS) innovations to patients. Strategically deployed, NAMs enhance the predictive value of preclinical studies for human outcomes while reducing reliance on animal models. Current scientific community interest focuses particularly on human-based and -derived systems, in silico and AI-driven models, and advanced microphysiological platforms, reflecting a shift toward human-centric drug development paradigms. Despite this momentum, significant challenges remain, including NAM reproducibility and validation, the establishment of standardized performance criteria, data sharing, and the evolution of regulatory frameworks needed to enable consistent adoption across the neurotherapeutics continuum. Nevertheless, there is a rich history of developing and adopting methodologies, particularly for improving the prediction of neurotherapeutic safety profiles while reducing animal use, and for advancing understanding of drug delivery across the blood–brain barrier, and the assessment of adverse neurological effects. These advances have begun to influence regulatory decision-making and are increasingly reflected in guidance and review practices. Furthermore, NAMs are showing concrete impact in neurological disorders, including Epilepsy, Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease, where human-relevant models and computational approaches support more precise characterization of disease mechanisms and therapeutic responses. In this paper, we examine the current and emerging roles of NAMs in neurotherapeutics development from government, academia, and industry perspectives, highlight key opportunities and limitations, and discuss the scientific, technical, and regulatory steps required to fully realize their potential in accelerating safe and effective CNS therapies.
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BibTeX
@article{tamiz2026approach,
title = {{New approach methodologies in neurotherapeutics development}},
author = {Amir P. Tamiz and Szczepan W. Baran and Thomas Hartung and Wendy W. Wu},
journal = {Neurotherapeutics},
year = {2026},
month = oct,
doi = {10.1016/j.neurot.2026.e01056},
url = {https://doi.org/10.1016/j.neurot.2026.e01056},
note = {CC BY},
}
RIS
TY - JOUR
TI - New approach methodologies in neurotherapeutics development
AU - Amir P. Tamiz
AU - Szczepan W. Baran
AU - Thomas Hartung
AU - Wendy W. Wu
PY - 2026
DA - 2026/10/24
JO - Neurotherapeutics
DO - 10.1016/j.neurot.2026.e01056
UR - https://doi.org/10.1016/j.neurot.2026.e01056
AB - New Approach Methodologies (NAMs) offer substantial opportunities to transform neurotherapeutics discovery, optimization, and development, reducing the timeline to translate central nervous system (CNS) innovations to patients. Strategically deployed, NAMs enhance the predictive value of preclinical studies for human outcomes while reducing reliance on animal models. Current scientific community interest focuses particularly on human-based and -derived systems, in silico and AI-driven models, and advanced microphysiological platforms, reflecting a shift toward human-centric drug development paradigms. Despite this momentum, significant challenges remain, including NAM reproducibility and validation, the establishment of standardized performance criteria, data sharing, and the evolution of regulatory frameworks needed to enable consistent adoption across the neurotherapeutics continuum. Nevertheless, there is a rich history of developing and adopting methodologies, particularly for improving the prediction of neurotherapeutic safety profiles while reducing animal use, and for advancing understanding of drug delivery across the blood–brain barrier, and the assessment of adverse neurological effects. These advances have begun to influence regulatory decision-making and are increasingly reflected in guidance and review practices. Furthermore, NAMs are showing concrete impact in neurological disorders, including Epilepsy, Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease, where human-relevant models and computational approaches support more precise characterization of disease mechanisms and therapeutic responses. In this paper, we examine the current and emerging roles of NAMs in neurotherapeutics development from government, academia, and industry perspectives, highlight key opportunities and limitations, and discuss the scientific, technical, and regulatory steps required to fully realize their potential in accelerating safe and effective CNS therapies.
SN - 1878-7479
SN - 1933-7213
ER -