Neurodegeneration Workshop Report


On March 6-8, 2006, the NIH Blueprint for Neuroscience Research hosted a workshop to generate ideas for FY 2007 initiatives and activities. The NIH Blueprint for Neuroscience Research is a collaborative effort among the NIH Office of the Director and fifteen Institutes and Centers to accelerate research on the nervous system. By pooling resources and expertise, the Blueprint takes advantage of economies of scale, confronts challenges too large for any single Institute and Center, and develops research tools and infrastructure that serve the entire neuroscience community.

The Blueprint has identified three broad themes of interest to all of the participating Institutes and Centers: neurodegeneration, neurodevelopment, and plasticity. Blueprint initiatives will focus on neurodegeneration in FY 2007 and on neurodevelopment and plasticity in subsequent years. Neurodegeneration occurs in classical neurodegenerative disorders such as Alzheimer's and Parkinson's disease, in macular degeneration and other disorders of sight and hearing, in drug and alcohol abuse, and perhaps in mental disorders and chronic pain. As our population ages, the already enormous impact of neurodegeneration on society will become even larger without better prevention and treatment. Developing strategies to prevent degeneration of neurons and to promote a healthy nervous system is thus critical to the missions of all Blueprint members.

The Blueprint neurodegeneration workshop brought together approximately thirty scientists from a broad range of disciplines and perspectives to consider research tools, resources, and training activities that could accelerate progress in neurodegeneration research. During the workshop, four breakout groups discussed and formulated recommendations on the causes of neurodegeneration, pathophysiology, diagnosis, and treatment. When the meeting participants reconvened to share the conclusions of their breakout sessions, several common themes and recommendations emerged:

  • Provide a mechanism, with accelerated review, to encourage highly innovative research that could have a profound impact on the field of neurodegeneration
    Despite many years of research by a sizable and talented scientific community, progress toward understanding and treating neurodegenerative disorders has been discouragingly slow and incremental. A rapid influx of bold new ideas might reinvigorate the field. Most current NIH grant mechanisms and review practices favor conservative grant applications and can take a year or longer from application receipt to funding. The Blueprint should develop a program to support high-risk/high-payoff research applications with accelerated review.

  • Better coordinate and publicize existing NIH programs in therapeutics development and develop new research tools and resources to address gaps
    A major roadblock in neurodegeneration research is translating discoveries about the biology of neurodegeneration into treatments. While the NIH has many programs that support drug development, including some focused on neurological disorders, it can be overwhelming for a researcher to navigate the various options and identify those that are most appropriate. Some aspects of therapeutics development may not be addressed sufficiently by current NIH programs, including medicinal chemistry, pharmacokinetics/ pharmacodynamics, drug formulation, and the challenge of delivering therapeutics across the neurovascular unit (blood-brain barrier) or to particular cell populations. Promising new approaches in gene and cell-based therapies could benefit from research tools such as RNA silencing libraries, viral vectors, and standardized cell lines. The Blueprint should provide a more effective way of navigating existing therapy development programs and develop new programs, tools, and resources where they are lacking.

  • Develop and distribute improved animal and cellular models of neurodegeneration
    Researchers need better cellular and animal models of neurodegeneration (including invertebrates) to investigate the biology of neurodegeneration and to conduct preclinical studies of potential interventions. Appropriate models are needed to study the molecular basis of the disease, the symptoms, and long-term progression. NIH sharing policies must be enforced effectively in order to make the best use of existing models. The Blueprint should improve access to existing models and foster the development of new models to address specific scientific questions in neurodegeneration.

  • Provide access to biological materials at different stages of disease, matched controls, clinical correlates
    It is vital that researchers have easy and rapid access to human tissue (brain tissue, DNA, cells, blood, cerebrospinal fluid, fibroblasts/skin) for studies on the pathophysiology and cause of neurodegeneration. Tissues must be available in an appropriate quantity, with detailed phenotypic information about the patient and matched control samples. A database containing biological and phenotypic information could help researchers generate new hypotheses and accelerate progress towards therapies.

  • Develop ancillary studies to large, ongoing epidemiology projects to collect neurodegeneration data
    Large-scale epidemiology studies can provide valuable information about neurodegeneration risk factors but can also be prohibitively expensive. The Blueprint should encourage the collection of neurodegeneration data through collaborations with large studies that have already established the appropriate infrastructure.

  • Identify and validate biomarkers/biosignatures for neurodegeneration
    Diagnosing neurodegenerative conditions before symptoms appear and irreversible cellular damage is done may be essential to effective treatment. Early markers of neurodegeneration would also aid preclinical and clinical studies and reduce the time and cost of evaluating interventions. Markers predictive or indicative of neurodegeneration could be molecular, behavioral, or imaging-based. Signature markers are needed for specific diseases and for neurodegeneration more broadly, in humans and in animal models. It is especially important that markers be "vertically integrated," i.e., a marker in an animal model should have a correlative marker in humans.

  • Catalyze new interdisciplinary research communities
    Progress in neurodegeneration research will require the integration of ideas and data from scientific communities that may have seldom collaborated in the past. Researchers who study behavioral biology, cellular neuroscience, genetics, epidemiology, chemistry, and informatics often work in different departments. Basic scientists and clinicians who study neurodegeneration often do not have opportunities to interact. Even researchers in similar disciplines who focus on different neurodegenerative conditions typically work in different professional circles. Creating connections across disciplines will help stimulate new research ideas and accelerate progress. Workshop participants offered various suggestions for ways to catalyze interdisciplinary research teams and approaches. Several strategies focused on training of the next generation of neurodegeneration researchers. For example, the Blueprint could offer incentives for trainees to have two mentors from different disciplines. The Blueprint could also continue to train PhD researchers on human disease issues and lower the barriers that discourage medical students from pursuing a research career. Web-based training modules and virtual communities, workshops, and public-private partnerships were also proposed.

  • Develop tools to collect, analyze, and integrate large and/or diverse data sets
    In order to conduct truly interdisciplinary research, tools must be developed to collect and analyze diverse types of data in an integrated way. Standards for data acquisition and controls would also enable data sets from different research groups to be analyzed together. Bioinformatics training is also necessary for both new and current researchers.