Senate Subcommittee on Labor-HHS-Education Appropriations
Statement by Story C. Landis, Ph.D., Director, National Institute of Neurological Disorders and Stroke
William Beldon, Acting Deputy Assistant Secretary, Budget
Mr. Chairman and Members of the Committee:
I am Story Landis, Director of the National Institute of Neurological Disorders and Stroke (NINDS). I am pleased to present the President's budget request for NINDS for Fiscal Year 2005. The fiscal year (FY) 2005 budget includes $1,546,623,000, an increase of $44.9 million over the FY 2004 enacted level of $1,500,693,000 comparable for transfers proposed in the President's request.
The mission of the NINDS is to reduce the burden of neurological disorders by finding ways to prevent or to treat these diseases. When I began as Director about six months ago, one of my first priorities was to meet with voluntary groups representing patients and their families. So far, I have met with more than 40 groups, and this remarkable experience has educated me about the extraordinary range of diseases within the NINDS mission, the power of their impact, and the urgency of finding ways to prevent or treat these disorders. These discussions also reinforce the importance of increasing public-private partnerships, which is a goal of our Institute, as well as a major focus of the NIH Roadmap process.
My own research has focused on fundamental questions about how the nervous system develops-how genes help wire up connections in the brain, how cells choose to become a particular type, and whether there is any "plasticity" in this process. Issues such as these, long central to basic neuroscience research, are now at the crux of efforts to devise treatments for neurological diseases. I am encouraged by the prevention and treatment strategies emerging from the investment in basic research-drugs to home in on the molecules that cause disease, stem cells to repair the damaged nervous system, natural neurotrophic factors to promote survival and growth of brain cells, "vaccines" to prevent stroke, implantable stimulation devices to compensate for brain circuits unbalanced by disease, therapies to turn off, repair or replace defective genes, neural prostheses to read control signals directly from the brain, and behavioral and drug interventions to encourage the "plasticity" of the brain and spinal cord to compensate for damage. The NINDS must continue to support basic research. We must also re-energize our efforts to translate opportunities into practical therapies. Today I will highlight a few of the ways we are working to bring people and resources together to accomplish that.
Neural stem cell biology is one area in which basic science and clinical promise are so closely intertwined that it is easy to forget the origins of our understanding of neural stem cells in very basic research. The generation of new neurons in the adult brain was discovered when a basic scientist sought to understand how male canaries learn a new song each spring. This year, NINDS researchers have contributed to advances in identifying and isolating adult neural stem cells, in understanding the signals that control embryonic and adult neural stem cells, and in developing stem cell therapies in animal models that show promise for Parkinson's disease, demyelinating diseases, such as Canavan, Krabbe, or Tay-Sachs, and many other disorders. The NINDS has helped foster research on embryonic and adult stem cells through several initiatives, including training programs in the use of approved human embryonic stem cells, grant supplements to compare these to cells from other sources, and scientific workshops. An NINDS intramural researcher also leads a new NIH facility that is characterizing the approved human embryonic stem cell lines. For the coming year, an initiative targeting collaborative research in stem cell biology, designed to bring together teams of experts from several areas of stem cell biology, is a high priority.
Genetics is another neuroscience research area that has made astonishing progress. Overall, researchers have identified more than 200 genes that can cause neurological disorders. Gene findings in the past year are relevant to diseases such as Parkinson's disease, Charcot-Marie-Tooth disorder, and cerebral cavernous malformations, which can predispose people to strokes. Discoveries such as these lead to improved diagnosis, development of animal models, and the first clues to what underlies disease processes and how to stop them.
Several NINDS efforts bring people and resources together in genetics. Some are simple, but important, such as programs to promote sharing of transgenic mice that are essential models of human diseases. Others are more ambitious, such as the Gene Expression Nervous System Atlas (GENSAT) project, which will map the activity of thousands of genes in the brain and provide genetically engineered mouse strains that allow scientists to study how these genes contribute to health and disease. Microarray screening centers make another new technology and the data arising from it widely available. Microarrays allow scientists to simultaneously monitor the activity of virtually all genes, with wide potential applications to basic and clinical neuroscience; for example, recent studies show micrarrays may predict which patients will respond to approved drugs for multiple sclerosis. The NINDS Human Genetics Resource Center, established this year, makes DNA samples, immortalized cell lines, and accompanying clinical and pedigree data available to all qualified researchers. The repository currently contains samples related to stroke, epilepsy, Parkinson's disease, and motor neuron diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).
"Translational research" encompasses the many steps that are needed to move from basic research insights to a therapy that is ready for human testing in clinical trials, and the NINDS has a long history of programs in this arena. For example, over three decades, the Neural Prosthesis program has supported research on electronic and mechanical devices that help compensate for abilities lost through disease or injury, including pioneering research on direct brain control of prostheses, which has recently become a focus of such forward thinking agencies as the Defense Advanced Research Projects Agency (DARPA). The NINDS has responded to increasing opportunities by developing a comprehensive translational research program that fosters cooperative efforts, provides peer review criteria tailored to the needs of translational research, and utilizes milestone driven funding, which is common in industry. In FY 2003, the Institute funded the first projects in this program, focused on gene and stem cell therapies for Parkinson's disease, neuroprotectants for stroke and trauma, treatments for brain tumor, and drugs for epilepsy, ALS and Huntington's disease.
New and expanding efforts to develop drugs complement the broad translational program. The NINDS has awarded a contract for a high throughput screening (HTS) facility, and solicited proposals for the development of disease-related screening tests. HTS uses robotics to rapidly test large numbers of chemicals to find lead compounds for drug development and use as research tools. Ongoing screening efforts focus on ataxia telangiectasia, ALS, and Parkinson's disease. Several NIH institutes are working together to develop chemical libraries focused on the brain, and the NIH Roadmap "Molecular Libraries" component will directly facilitate screening efforts such as these.
Another NINDS drug development effort is a longstanding public-private partnership. Since 1975, the NINDS Anticonvulsant Screening Project has worked with more than 140 companies and 230 academic institutions to test more than 20,000 compounds for anti convulsant properties, including several drugs now in clinical use. Guided by the epilepsy benchmarks planning process, the Institute is expanding this program with increased focus on preventing the development of epilepsy and on treatment resistant epilepsy. The NIH Roadmap "Structural Biology" goals to improve our understanding of membrane proteins, such as ion channels that are implicated in some types of epilepsy and neurotransmitter receptors that are often the targets for drugs, will have an important impact on future efforts to develop drugs for this and many other neurological disorders.
Some drugs developed for epilepsy have shown promise for other diseases, such as chronic pain. To take advantage of that kind of crossover, observed in many areas of medicine, the NINDS worked closely with academia and voluntary disease organizations to develop a consortium of 26 laboratories to screen a set of 1040 known drugs, mostly approved by the U.S. Food and Drug Administration (FDA) for other uses, for potential use against neurodegenerative diseases. The Consortium is sharing data on 29 laboratory screening tests based on molecules, cells in culture, or simple organisms. Several promising drugs have moved to further testing in animals, and a few may move soon to clinical trials.
Valproic acid is one example of a drug, now used for the treatment of epilepsy, that in the past year has shown promise in cell culture for a different disease, spinal muscular atrophy (SMA). SMA is the most common single gene cause of infant mortality. In recent years, scientists have discovered the gene defects that cause SMA, developed animal models that mimic essential aspects of the human disease, and devised plausible strategies for developing therapies. Because of the impact of SMA and the state of the science, the NINDS chose this disease as the focus of an innovative approach, initiated in FY 2003, to expedite the development of therapies. The performance-based contract mechanism accelerates all steps from recognition of a research need, through solicitation and review, to funding of targeted research subprojects, with guidance by an expert steering committee that takes a very active role in driving the process. If successful, this approach might be applied to other diseases.
The muscular dystrophies are another group of inherited disorders that are a high priority for NIH. Researchers, beginning more than a decade ago, have identified defects in several genes that can cause the various kinds of muscular dystrophy. These findings have brought improved understanding of what causes these diseases, better animal models to develop therapies, and some practical benefits-for example, a new diagnostic test for Duchenne muscular dystrophy will eliminate the need for painful muscle biopsy in many children, and help identify female carriers of the disease before they pass it on to their sons. Therapies to slow or stop muscular dystrophies have been elusive, but there have been encouraging results recently in animals using drugs, stem cells, and gene therapy approaches. To expedite progress against the muscular dystrophies, the NIH has funded three Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers, with the expectation that up to three more will be funded competitively in FY 2005. The NIH is also working together with the broadly representative interagency Muscular Dystrophy Coordinating Committee (MDCC) on developing a muscular dystrophy research and education plan for NIH.
The NINDS, often working with other components of NIH, has several centers programs, such as the Morris K. Udall Parkinson's Disease Centers of Excellence, the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS), the Studies to Advance Autism Research and Treatment (STAART), and the Specialized Neuroscience Research Program (SNRP), which encourages minority scientists and addresses health disparities in neurological disorders. Other centers focus on disorders such as brain tumor, spinal cord injury, and head trauma.
The NINDS continues to set standards of quality and innovation in clinical trials that evaluate whether potential treatments or preventive measures are safe and effective. One recent example, the Neuroprotection Exploratory Trials in PD (NET PD), was launched in April 2003 to evaluate drug therapies that might slow the progression of Parkinson's disease. The project rigorously selected candidate drugs from a broad array of potential compounds identified by working with clinicians and researchers throughout academia and industry. The 42 clinical sites have recruited individuals with early, untreated Parkinson's, and early phase trials of four drugs will be completed in early 2005. In the coming year, the NINDS clinical trials program is also working to train researchers to conduct clinical trials and to develop a broad clinical trials network that will encompass the greater community of neurologists. Clinical trials for neurological disorders is another area in which the cross-cutting NIH Roadmap efforts for "Re-engineering the Clinical Research Enterprise" are likely to have a major impact.
Before becoming the director of NINDS, I led the Institute's intramural program on the NIH campus in Bethesda, MD, which is one of the largest basic and clinical neuroscience programs in the world. In addition to recruiting superb individual scientists in fields such as ion channels, genetic diseases of the nervous system, brain tumors, and stroke, a central focus of the program has been to bring researchers together from disparate fields of science. To this end, the Porter Neuroscience Research Center, opening its first phase in 2004, brings together scientists from eight institutes to "put the brain back together" by overcoming artificial disciplinary boundaries within and across institutes and by setting the standard for collaborative research in neuroscience.
I have mentioned a few areas in which the NIH Roadmap efforts will facilitate our efforts against neurological diseases, but the same can be said of virtually every major effort within the Roadmap. Driven by the science, several NIH components that have a major focus on the brain are also increasingly working together to form a "blueprint for the brain," in which cooperative efforts across Institutes can expedite progress. These Institutes already cooperate extensively in areas such as training of researchers, genetics, autism, muscular dystrophy, health disparities, brain tumors, stroke, and pediatric neuroimaging, to name a few examples. I hope to report to you in the future about progress in forming other cooperative ventures aimed at our common goal of finding better ways to prevent or to treat all disorders that affect the brain and other parts of the nervous system.
Thank you, and I would be pleased to answer questions.
Last Modified March 14, 2012