As a second source of input toward a "Blue Sky" vision for the future of neuroscience, the NINDS convened members of its staff as well as representatives from other NIH institutes for a workshop on May 31, 2007. Break-out groups discussed similar questions to those posed in a Request for Information (RFI) to the larger neuroscience community. In particular, they focused on anticipated advances in neuroscience and neurology over the next fifteen years, infrastructural and technological needs, challenges and research questions with significant potential impact for understanding nervous system function or the treatment and prevention of disease, and the role of NINDS in the neuroscience research landscape of the future. (The full text of the questions posed at this workshop appears at the end of this document.) After the workshop, NINDS staff framed the input received into the following broad topic areas.
Enable early and routine diagnosis of neurological conditions
- Determine an individual's risk for particular neurological disorders based on genomic markers, gene expression, or other measurable indicators (e.g., at birth and/or annual physicals, everyone receives a read-out of his or her neurological risk factors and recommendations for preventive actions)
- Develop technologies that primary care physicians, emergency workers, or even you, yourself, can use routinely to monitor your neurological heath and detect and diagnose neurological disorders at early stages when intervention is most promising (e.g., anatomical and functional scans are sufficiently affordable and user-friendly to become a routine part of an annual physical; the next generation of PDAs include personal neurological sensors)
- Develop and validate surrogate markers that reflect disease progression and can show, early on, whether therapies are working
- Develop technologies that will provide more patients with timely access to neurological expertise, even if a neurologist is not immediately or locally available (e.g. telemedicine, artificial intelligence-guided diagnostic alerts)
Develop new therapeutic strategies
- Develop neuroprosthetic devices that integrate with the brain to restore sensory, motor, or cognitive functions lost through disease or injury.
- Develop endovascular devices to restore blood flow to the brain in people who have ischemic stroke or compromised vascular flow that puts the brain at risk.
- Develop techniques that allow neurosurgeons to fix the brain with minimal collateral damage (e.g., robotics, remote targeting, nanoscale deep brain stimulation)
- Develop broadly applicable techniques or vehicles to deliver therapeutics into the brain and target particular cells or regions.
- Cure someone of a neurological condition with a gene therapy strategy that can be readily adapted to other neurological conditions.
Accelerate the process of therapy development
- Develop rational and generic ways to test the synergistic effects of combination therapies so that this becomes a routine aspect of therapy development.
- Develop a more rational and modular pathway for developing therapies, with a greater emphasis on design than screening (e.g., once a plausible drug target is identified, derive a 3-D structure, computationally predict ligand qualities, synthesize and test the ligand against off-the-shelf human cell assays and in validated animal models of efficacy and toxicity, and test clinically with surrogate markers)
- Develop strategies and infrastructure to enable any patient with a neurological condition to participate in a clinical trial (e.g., clinical trials become a routine option for patients, as in the cancer field)
- Establish strategies and infrastructure that will enable neuroscience researchers to more easily draw upon clinical observations in medical practice and from unpublished clinical studies (e.g., epidemiology and natural history data can be culled from electronic medical records; repository of negative data from clinical trials; interdisciplinary clinician teams provide medical care and conduct research)
- Develop strategies and/or infrastructure to conduct pilot clinical trials more efficiently
Understand the healthy nervous system
- Identify the cellular and molecular mechanisms of plasticity responsible for particular behavioral changes.
- Determine the extent of brain plasticity, its consequences in normal function, and how to harness it for healing.
- Determine how percepts, memories, and other aspects of cognition are represented in brain cells, circuits, and synapses and how neural circuits perceive, execute movement, regulate bodily functions, remember, think, emote and carry out other functions.
- Determine how gene expression influences nervous system function and vice versa
- Determine the role of cell-cell interactions in regulating neurodevelopment
- Understand the natural aging process and its relationship to development
- Understand lipid-protein interactions and their potential as drug targets
- Determine the roles of glia
- Determine the functions of sleep
- Understand the mechanism, function, and regulation of protein folding (e.g., predict the 3-D structure from the sequence and design a protein with a novel and useful structure)
- Determine the extent and function of adult neurogenesis (e.g., is it involved in learning? Recovery from cell loss?)
- Determine the interactions between the healthy brain and body
Understand neurological disease
- Determine common mechanisms that contribute across diseases, and classify diseases by underlying mechanisms rather than symptoms.
- Determine why people get the diseases they do (i.e., how genes, environment, and chance interact and conspire)
- Determine the interactions between the brain and the body in disease states
Develop new technologies for observing the nervous system
- Develop technologies to monitor the activity of many individual neurons simultaneously, over long periods of time, in behaving animals, including people
- Develop technologies to image at the molecular level in vivo, in real time
- Develop a complete anatomical connectivity map of the human brain
Develop new strategies to probe neural functions
- Develop models of the human nervous system that can predict responses to natural or experimental perturbations
- Develop the ability to control the timing and location of gene expression.
- Develop the ability to control neural activity at the single cell level, in behaving animals
Improve strategies for data collection and analysis
- Develop methods to understand how the many parts work together, whether in gene expression, signal transduction, neural circuits or any neural system
- Develop infrastructure and strategies to make published and unpublished data widely available and easily useable by other laboratories (e.g., integrated databases with defined standards for data collection and analysis)
The workshop discussions also generated a number of additional ideas that are less directly related to the goals above but that suggest changes in policies and practice with the potential to benefit NINDS and neuroscience research in the future.
- NINDS routinely hands off projects to industry
- Widely available data analysis services
- Research tools widely available, including easy access to novel compounds
- Academic research centers value teams and collaborative research groups
- Funding mechanisms and infrastructure enable large-scale collaborative research across disciplines
- Young researchers have the training they need to fill the biomedical research positions in highest demand, which will likely be in translational research
- NINDS as a world leader that brings together major research supporters to identify common goals and collaborative strategies to achieve them; encourages widespread sharing of data and resources; and brokers interactions between academia, federal agencies, patient groups, foundations, industry, and other businesses
- The US establishes collaborative partnerships with scientists in other countries and helps to foster a global research network
- Existing resources and resources are maximally utilized and adapted for new purposes (for instance, infrastructure exists where existing techniques are tested, developed and distributed)
- Academic medical centers restructured and less reliant on NIH funding
- Infrastructure support separate from research project support
Full text of questions posed at the internal NINDS Blue Sky Meeting
What advances should we expect in clinical care for neurological disorders over the next fifteen years, based on anticipated progress in biomedical research? What scientific advances will result in a quantum leap in the care of neurologic disorders, and what aspects of care are likely to remain unchanged?
The past fifteen years has seen major shifts in how clinicians diagnose, treat, and prevent neurological conditions:
- Brain imaging and genetic technologies have changed how many neurological conditions are diagnosed.
- The first effective emergency treatment for stroke is transforming acute stroke care, and continued progress in stroke prevention is having a major impact on public health.
- New surgical interventions, such as deep brain stimulation, have emerged, with potentially wide-spread uses. Fifteen years from now, we hope to have better interventions for all neurological conditions. The NINDS will systematically review basic, translational, and clinical opportunities to accomplish this. Please consider scientific trends and crosscutting medical advances to which NINDS research should contribute.
Which major questions need to be answered in order to revolutionize how we understand the nervous system and prevent, diagnose, and treat nervous system disorders?
Several major discoveries over the past fifteen years have revolutionized how we understand the nervous system and its disorders. New insights into the development of the nervous system, brain plasticity, molecular pathology, and the role of non-neuronal cells, for example, are already changing how we think about the brain and treat maladies. What mysteries about how the nervous system develops and functions will be the subject of major advances in the next fifteen years?
What new technical capabilities have the potential to revolutionize neuroscience research and clinical practice in the next fifteen years?
Advances in neuroscience knowledge frequently come on the heels of technological advances, providing the means to answer questions that were previously inaccessible. Patch clamp recording, gene splicing, genetically modified mice, and advanced neuroimaging are just a few of the techniques and tools that have opened up remarkable new possibilities in the clinic and at the bench. What major technical roadblocks could be overcome in the next fifteen years, and what might be the impact on research and practice?
What will the neuroscience research landscape look like in fifteen years, and how can NINDS best contribute?
The NINDS is only one participant of many in the broad neuroscience research enterprise. In the past fifteen years:
- New NIH Institutes and Centers have been established, others have changed their focus, and trans-NIH programs including the Blueprint for Neuroscience and the Roadmap for Medical Research have taken on important roles.
- New neuroscience research institutes have been formed worldwide.
- The biotechnology sector has dramatically expanded, and the pharmaceutical industry has undergone major restructuring.
- Patient groups have become more active in supporting research. How will the biomedical enterprise evolve over the next fifteen years, and what niche should the NINDS occupy? How should the NINDS operate in this landscape to support the range of neuroscience research, inform the public about the results of that research, train new scientists, and build the infrastructure required for scientific advancement?
What, if any, infrastructural resources are needed to advance clinical or basic neuroscience research?
In the past fifteen years:
- The Human Genome Project has developed resources, such as GenBank, that have transformed research, and the NIH Roadmap for Medical Research is developing common resources to enable research that might otherwise not occur.
- The NINDS has invested in resources such as a publicly accessible genetic database for neurologic diseases, clinical trials networks, microarray centers, a Human Genetics Repository, and a variety of programs with other NIH institutes in the NIH Blueprint for Neuroscience Research. What resources do you consider valuable, and which are no longer needed? What new neuroscience resources are essential to accelerate the pace of discovery over the next fifteen years?
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