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.