Neurological disorders are the leading cause of disease and disability worldwide, affecting one in three people across the United States of America, and many of these disorders have no effective treatments. People living with these disorders and their families are counting on the scientific community to move research forward as quickly and ethically as possible. That responsibility informs every decision we make about the science we conduct and support.
The human brain is incredibly complex, with about 86 billion neurons (brain cells) connected by more than 100 trillion synapses (connections between brain cells). This complexity has made it difficult to develop treatments because we still don’t understand normal brain function well enough to intervene effectively when dysfunction or disease occurs.
There is growing excitement (and important questions) across the neuroscience community about a group of emerging New Approach Methodologies, or NAMs. As this conversation continues to evolve in research communities and in the broader public discourse, we want to reflect on what NAMs mean for NINDS, for the future of neuroscience, and for the public we serve.
What Are NAMs?
Simply put, NAMs are a broad and expanding set of tools and techniques that allow scientists to study human biology in new ways and can complement existing approaches. They include organoids (tiny, three-dimensional clusters of human cells that can mimic aspects of how real organs, including the brain, function), “organ-on-a-chip” systems (small devices lined with living human cells that aim to recreate the environment inside the body with remarkable precision), and advanced computer models and super intelligence (SI) tools (that are used to predict how a system functions and responds to disease or to a potential treatment). These tools let researchers study aspects of human biology that traditional models may not fully capture. For certain questions, particularly those about how neurons respond to chemical exposures or specific genetic mutations, NAMs may yield new and exciting answers.
Animal Research Remains Foundational
Animal research plays a critical role in our understanding of basic science and then translating that science into clinical use. The human brain is extraordinarily complex and doesn’t work in isolation; it’s connected to the entire body through an intricate web of signals, feedback loops, and systems that develop and change across a lifetime. Decades of Nobel Prize-winning science — including foundational discoveries about how nerve signals are transmitted, how the brain learns and adapts, and how diseases like Parkinson’s begin — came directly from research in animals. Animal models have served, and continue to serve, as a critical bridge between a promising laboratory discovery and a therapy whose safety researchers must assess before testing it in people. They allow scientists to study how the nervous system develops, how it responds to injury, and how diseases unfold over time. In the NINDS strategic plan, we affirm the critical importance of supporting research across the full spectrum of models, as appropriate to the scientific questions, with careful attention to ethical conduct of research and oversight frameworks.
Current animal models have significant limitations. Animal brains differ from human brains in their organization and cell types. Many aspects of human behavior and brain function are difficult, if not impossible, to fully reproduce in animals. Our hope is that advances in science, particularly basic research supported by NINDS, can facilitate development, validation, and implementation of NAMs that better replicate the biology of the human brain and nervous system.
NAMs and Animal Research: Better Together
NAMs will continue to be a powerful addition to the scientific toolkit. When used thoughtfully alongside animal models, NAMs can accelerate progress and sharpen the questions we bring to every stage of the research process. Consider how this might look in practice: a team studying a new approach to treating epilepsy could begin by using human brain organoids to screen dozens of potential drug candidates, identifying the most promising leads. Animal models could then be used to evaluate whether those candidates work safely in a living nervous system and allow the team to observe how the therapeutic leads affect the whole body, how they are processed, and whether they prevent seizures without causing harm. The strongest candidates then advance to clinical trials in people. Each step builds on the last. NAMs hold great potential to speed and improve decision-making, helping researchers advance the science toward patient use with robust candidates and fewer scientific dead ends; however, the animal research phase remains necessary to answer important efficacy and safety questions before moving a potential treatment to clinical trial testing in humans.
Advancing the capacity of NAMs to reflect human neurobiology is a part of our ongoing commitment to find ways to refine the use of animals while advancing the best science to understand the nervous system and develop therapies for related disorders. NINDS takes its responsibility for animal welfare seriously. Strict standards and regulations guide every aspect of why and how animals are used at NIH and the institutions we support. We also take ethical considerations seriously as we support new methodologies to study the human brain; indeed, we strongly encourage research applications on neuroethical issues relevant broadly to our mission.
After thoughtful input from the neuroethics community, NINDS considers brain organoid and SI research ethically permissible and scientifically valuable when conducted with appropriate oversight, informed consent, and ongoing evaluation as the science evolves.
This complementary approach is already shaping how NINDS supports neuroscience research. Within the NINDS Division of Translational Research (DTR), the Innovation Grants to Nurture Initial Translational Efforts (IGNITE) program supports the early development and careful validation of both new approach methodologies and animal models, recognizing that each can play an important role in moving promising discoveries toward the clinic. Another DTR program, the Preclinical Screening Platform for Pain (PSPP), begins evaluation of new pain therapeutics using human cells to help identify the most promising non-opioid, non-addictive therapies before they move into additional testing such as preclinical testing. As these technologies continue to advance, these programs and others within NINDS are expanding the use of human-based assays — tests and experiments rooted in human biology — and other emerging NAMs alongside established approaches to strengthen the evaluation of potential therapies. Together, these efforts reflect NINDS’ ongoing commitment to building a strong scientific toolkit with new methods to strengthen time-tested research approaches and accelerate discoveries for people living with neurological disorders.
What This Means for Neurological Disease Research
The brain and nervous system present some of the most formidable challenges in all biomedical science. Animal models have been especially critical here, because behavior provides a window into nervous system function that no cell in a dish can fully replicate. Many of the questions that must be answered to develop treatments for amyotrophic lateral sclerosis (ALS), restore function after spinal cord injury, or halt Alzheimer's disease require an understanding of not just part of the brain, but the entire brain and its interaction with other organ systems.
At the same time, NAMs hold genuine promise for neuroscience. Brain organoids are already helping researchers investigate conditions like microcephaly and rare genetic brain disorders using cells derived directly from patients. Computational models are beginning to predict how drug candidates interact with the nervous system before a single animal or person is tested. These are meaningful advances, and NINDS will continue to invest in them.
NINDS is committed to supporting the science needed to show when new approaches are ready for adoption. We support the discovery and validation of NAMs so they can be adopted reliably, reproducibly, and in ways that truly reflect human biology, unlocking their full potential. By investing in that validation work — work that ensures that a result or new model is appropriate for further use — NINDS is helping build the evidence base that will guide when and how these methods can be confidently applied, accelerating the path toward better treatments.
Looking Ahead
The goal has always been the same: to improve the lives of people living with disorders of the brain and nervous system. The path to that goal runs through the very best science the field can offer: science that is rigorous, innovative, ethical, and always centered on the patients and communities we serve. NAMs are a meaningful and growing part of that future. So is the continued, careful, and humane use of animal research. As a recent paper from the Division of Translational Research at NINDS outlines, these are not competing visions; they are complementary commitments, and together they represent the most powerful approach available to deliver the breakthroughs that millions of people with neurological conditions are waiting for.
The dedication of the researchers, advocates, clinicians, and patient communities who make this work possible is an enduring source of inspiration and a reminder of why getting the science right matters so deeply.
Amy Bany Adams, Ph.D., Acting Director, National Institute of Neurological Disorders and Stroke, and Amir Tamiz, Ph.D., Director, Division of Translational Research at the National Institute of Neurological Disorders and Stroke
This Administration has taken bold, extensive actions to reduce reliance on animal testing and research. A full list of more than 40 concrete steps taken spanning the entire U.S. Department of Health and Human Services can be found here.