NINDS supports and performs a broad array of rigorous and important neuroscience research from fundamental studies of basic nervous system function to studies to improve treatments and prevent neurological disorders.
NINDS Strategic Plan home » Neuroscience Research
Table of Contents:
Understanding the healthy nervous system is the foundation for public and private sector progress in preventing and treating all neurological disorders and for maximizing brain health. Although the potential long-term benefit of this basic research for people with neurological conditions is a strong motivation for researchers, scientists’ natural curiosity about how the brain works and their insights into which questions may hold the key to fundamental advances often drives new discoveries with benefits that were completely unanticipated. A single major basic science discovery, whether from experiments in single cells, simple organisms, laboratory animals, or people, has the potential to elevate research for a host of different diseases. Fundamental studies on how genes and the environment guide brain development, on chemical signals by which brain cells communicate, on mechanisms of electrical activity in the brain and spinal cord, on supporting cells in the nervous system, on the relationship between brain cells and their blood vessels (the “neurovascular unit”), on brain circuits that control complex behaviors, and on many other aspects of basic neuroscience underlie all of today’s and tomorrow’s treatments for neurological disorders. Similarly, the NINDS mission benefits enormously from basic research in many areas of science from across the NIH, the National Science Foundation, and other organizations.
NIH is and will continue to be the world’s leading supporter of basic neuroscience, with additional funding coming from disease organizations, private science foundations, and industry. Since the last NINDS Strategic Plan, NINDS has established an ongoing process to monitor the vigor of basic neuroscience research. The Institute has taken several actions to sustain these crucial lines of mechanistic, discovery research, including targeted funding for fundamental neuroscience, and published statements by the entire NIH leadership to the research community on the importance of basic research prompted by NINDS analyses. Engaging the diverse scientific perspectives and insights of thousands of scientists, engineers, and physicians to seek out the best opportunities to advance our understanding is the most effective path forward. Hence, NINDS will maintain its long-standing emphasis on investigator-initiated research, with targeted initiatives for individual investigators and teams to address opportunities or obstacles that investigator-initiated research is unlikely to address.
The BRAIN Initiative®, which is developing and applying new tools to understand how brain circuits process information, is the most ambitious basic neuroscience initiative ever undertaken. In 2019, a mid-course external review found that the Initiative is making significant progress on all major priorities of the plan, with many objectives accomplished, and unanticipated progress in some areas. Because of this remarkable progress, the review suggested that in addition to continuing the productive path underway, the Initiative could now invest in a few large-scale, transformative projects that might propel neuroscience far into the future. After assessing the feasibility and impact of potential transformative research, the Initiative is focusing on three projects: 1) a comprehensive atlas of cell types in the human brain (“parts list”); 2) creating a “wiring diagram” of the mammalian brain, beginning with synapse level “connectome” in mouse brain and the “projectome” of long- range pathways in human and non-human primate brains; and 3) developing an armamentarium of tools and resources to precisely access and modulate specific brain cell types, with the ultimate goal of precision medicine applications in humans.
Understanding what causes each neurological disorder and its subtypes, drives progression, and the factors that determine recovery are all essential for developing interventions to prevent or treat these diseases. Countless examples illustrate the value of understanding the underlying biology through the use of model organisms, tissue and cell platforms, and human subjects research for developing rational strategies to treat disease. Among these, for example: the discovery that dopamine, a brain signaling molecule, is lost in Parkinson’s disease led to therapy with the drug L-dopa; and studies on how changes in brain movement control circuits led to Deep Brain Stimulation therapies. The recognition that many brain cells can be rescued if blood flow is restored rapidly following stroke led to effective emergency stroke treatments. Finding that the immune system attacks the insulating covering of nerve fibers in multiple sclerosis was pivotal in developing today’s drugs that reduce symptoms and slow disease progression. The recent breakthroughs in gene targeted therapy for spinal muscular atrophy shows a path forward from recognition of underlying genetic causes for many other diseases.
As for basic research on the healthy nervous system, funding the highest quality investigator-initiated research grants will remain the Institute’s core strategy for understanding the causes and consequences of neurological disease. Based upon input from our stakeholders via requests for information and workshops, NINDS will also target solicitations for grants to address salient opportunities or obstacles to progress that may not be addressed by investigator-initiated research. Several ongoing programs in epilepsy, traumatic brain injury, Parkinson’s disease, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), spinal cord injury, dementias and cross-cutting resources illustrate these strategies.
Biomarkers are measurable indicators of normal biological processes, disease progression, or responses to therapeutic interventions. These “fit for purpose” measures improve care or accelerate the development of better therapies. By enabling researchers and physicians to see more precisely critical aspects of disease biology and response to treatment in individuals with a neurological condition, these indicators, together with development of more targeted therapies, can help get the right care to the right people at the right time. Biomarkers may enable early detection of disease, identify individuals who are most likely to benefit from a treatment, indicate whether a candidate drug has engaged the biological target it is designed to seek out, or determine whether underlying disease is progressing. Use of biomarkers in laboratory animal studies that translate directly to human clinical studies is especially valuable to accelerates development of treatments. Outcome measures assess the effects, both positive and negative, of an intervention or treatment on individuals living with neurological conditions and are essential for testing the effectiveness of treatments. Outcome measures must be informed by goals of people with neurological conditions. They include functional outcomes, including participation in activities of daily living, community integration, and patient-reported quality of life assessments, laboratory tests of many types, neuropsychological and cognitive assessments, and standardized clinical ratings by physicians or other health care professionals. Biomarkers and outcome measures provide an essential foundation for precision medicine. Basic research on disease mechanisms and observations by clinicians provide the initial impetus for the discovery and development of diagnostics, biomarkers, and outcomes measures. However, the path from a potential marker to one with the demonstrated reliability and validity to be useful in therapy development or patient care requires a different approach from discovery research. Several targeted NINDS biomarker programs systematically will build on opportunities arising from basic research or clinical observations to carry out the rigorous, focused development and validation of biomarkers and outcome measures that are necessary before they can be relied upon in drug development programs and clinical trials. NINDS will continue to improve and expand its biomarkers programs to capitalize on emerging opportunities.
NINDS basic research identifies targets for therapeutic interventions, that is, research reveals the key steps in the disease process at which a drug or other therapy might act to counteract disease with minimal unwanted effects. In addition, basic research enables the development and refinement of approaches to improve upon existing treatments. Basic research also develops animal models, research reagents, diagnostics, biomarkers, and outcome measures, all of which are essential for developing therapies. Beyond basic research, NINDS and the private sector have complementary roles in the development of treatments for neurological disorders, both in the preclinical (laboratory) and clinical stages. In the last several years, several large pharmaceutical companies have withdrawn entirely from development of therapies for nervous system dysfunction because of the enormous challenges entailed in developing drugs for the brain. The Institute will continue to monitor changes in private sector strategies and adjust its strategy accordingly to optimally complement, rather than compete with, the private sector.
NINDS will continue to support translational research from early preclinical therapy development through first-in-human studies for small molecule drugs, biologics (including cell and gene targeted therapies), and devices. The goal is to design interventions with mechanisms and delivery that are precisely targeted to intervene in the disease process how, when, where, and on whom the treatments can be most effective. The more innovative a therapeutic strategy and the greater the risk for failure, the further NINDS is likely to advance development and thereby de-risk the future investment by industry.
Although basic research scientists are eager to see their findings translated into therapies that can help people, few academic scientists have the expertise and resources to pursue such development in their own laboratories. Thus, in addition to supporting translational research via traditional investigator-initiated grant programs, NINDS drug and biologics programs will provide expertise and contract-based therapy development resources that are not usually available to academic and small business researchers. Similarly, beginning 50 years ago NINDS pioneered the development of devices to treat neurological disorders, and the Institute will continue its long-standing support for the development, optimization, translation, and first-in-human testing of therapeutic and diagnostic devices for disorders that affect the nervous or neuromuscular systems. Milestone-gated funding for more advanced therapy development projects enables NINDS to be an effective steward of resources, shifting funds to the most promising opportunities as warranted by progress. Here is information about all of NINDS’s translational research programs.
The recent advent of successful gene targeted therapies for a few rare genetic disorders heralds a new era for many devastating and heretofore untreatable neurological disorders, and NINDS will act aggressively to take advantage of these emerging opportunities. Many genetic neurological disorders are ultra-rare, in some cases only affecting a few people in the world. However, these disorders often have a devastating impact and collectively they impose a large, unmet need, affecting individuals across the age spectrum. The NINDS URGenT Network, now under development, will rapidly develop tailored therapeutic interventions using precision medicine platforms for the treatment of serious, life-threatening ultra-rare disorders. Although the challenges are daunting, a few remarkable examples have demonstrated that it is possible to develop therapies for ultra-rare disorders rapidly enough to benefit individuals with neurological conditions. The private sector is unlikely to take on this challenge, and thus this program is imperative for the Institute.
NINDS clinical research complements private sector clinical research and development. In addition to testing the safety and efficacy of innovative treatments for neurological disorders and stroke, the Institute supports epidemiological studies, testing of preventive interventions, comparison of existing therapies, exploration of new uses for existing treatments, evaluation of rehabilitation interventions, validation of biomarkers and outcome measures, and investigation of the causes of neurological disorders.
NINDS will continue to support early and advanced phase clinical trials and comparative effectiveness research of treatments and prevention for neurological disorders, as well as large epidemiological studies. The NINDS clinical research infrastructure, including clinical research networks, improves the efficiency and effectiveness of clinical trials, and the Institute will take advantage of innovations, including adaptive trial designs and data analytics, to carry out these studies most efficiently and effectively. The Institute also supports studies on the natural history of disease that will inform interventional trials. The Institute’s Common Data Elements project works with research and patient advocacy communities to develop data standards for neurological disorders that facilitate data sharing in a meaningful way and enhance data integrity. Interoperability is crucial as potential applications of data analytics and artificial intelligence interrogation of clinical data become more useful. Here is information about NINDS’s clinical research programs including currently available tools.
Progress in preventing stroke and promoting brain health has had a major impact on public health. However, despite reductions in stroke rates across all ethnic groups, significant stroke disparities persist across population groups, and stroke rates are apparently rising in younger persons after decades of improvement. Furthermore, the progress in preventing stroke has been the exception; there has been much less progress in preventing other neurological disorders. Basic research now underway provides the foundation for preventing other diseases, for example, by understanding why acute pain becomes chronic for some people and how brain trauma can result in epilepsy, and there are encouraging results from recent trials showing that progress in controlling major stroke risk factors may also slow the development of dementia. There is also increasing attention to the role of the environment, including stress, environmental chemicals, and a variety of other factors, relating to neurological disorders. Thus, both continuing the long-term progress in preventing stroke and promoting brain health and extending progress to other neurological disorders will remain high priorities for NINDS in the immediate future.
Neurological conditions affect people of all ages, races, ethnicities, sexes, genders, sexual orientations, gender identities, and disabilities, and can differentially affect individuals based upon these characteristics, as well as in association with geographic, socioeconomic, or other factors. NINDS is committed to understanding what drives health disparities across the lifespan and to reducing the burden of neurological disorders borne by underserved groups of society, including racial and ethnic minorities, rural, and socioeconomically disadvantaged populations, by funding a spectrum of research from basic science through clinical studies and through public health information programs. Because improving health equity is so important, and progress has been so challenging, the Institute has established a new Office of Global Health and Health Disparities in the Division of Clinical Research.
Led by this office, the Institute has embarked on a planning process focused on health equity, within the broader framework of the overall NINDS Strategic Plan. NINDS is seeking extensive stakeholder input to inform our research investments in this space. A Working Group of the National Advisory Neurological Disorders and Stroke (NANDS) Council, with several notable experts in health disparities research, has been charged with providing scientific guidance on how best to advance research on neurological health disparities and health equity, with an emphasis on addressing biologic, socio-demographic, economic, and other social determinants of health. Additionally, a recent Request for Information (RFI) to gather information from extramural researchers and the public on known areas of disparity/inequity in neurological disease, treatment, and provision of services across the lifespan yielded nearly 150 responses. The planning effort culminated in a public three-day virtual workshop held on September 22-24, 2021, as well as published reports of the planning process, findings, and research recommendations. This workshop is available on NIH Videocast.