Senate Subcommittee on Labor-HHS-Education Appropriations
Statement by Audrey S. Penn, M.D. Acting Director, National Institute of Neurological Disorders and Stroke
Mr. Chairman and Members of the Committee:
I am Audrey Penn, Acting 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 2004. The fiscal year (FY) 2004 budget includes $1,469 million, an increase of $13 million over the FY 2003 enacted level of $1,456 million comparable for transfers proposed in the President's request.
The mission of NINDS is to reduce the burden of neurological disorders, that is, the many diseases that affect the brain, spinal cord, muscles, and nerves of the body. Neurological disorders cause enormous suffering and loss of life, often defying the best efforts of modern medicine. However, we are making progress in prevention and in treatment, derived from continuing advances in fundamental scientific understanding of the nervous system, which enhance the prospects for the future. Today I will touch on these points and concentrate on what NINDS is doing to expedite progress.
Neurological disorders can compromise the complex thinking and emotions that make us human, the routine perception and movement that we take for granted, and even the control of bodily systems that are normally beneath our awareness. Diseases of the nervous system strike at every age. Some, such as stroke, chronic pain, epilepsy, and traumatic brain injury, are among the most common of all causes of death and disability. Hundreds of less common neurological disorders take an incalculable toll on patients and families too. Also demanding attention are substantial disparities in impact by ethnic group, gender, socioeconomic status, and geography.
Progress in preventing and treating neurological disorders has been notable. As Dr. Zerhouni has testified previously, this year alone almost a quarter of a million fewer deaths from stroke will occur in the United States than would have been expected without advances in prevention - progress that represents the cooperative efforts of many groups, public and private. Prevention of nervous system birth defects, such as spina bifida, and genetic counseling for inherited disorders, such as Tay-Sachs disease, are also having a major impact on public health. The first acute treatments for ischemic stroke and spinal cord injury - though still far from adequate - have proven effective for reducing neurological damage. Immune therapies now reduce relapses and slow the progression of disability in multiple sclerosis. Surgical options employ implantable devices to compensate for brain circuits unbalanced by disease in Parkinson's disease and epilepsy. Enzyme therapies have brought the first successes in treating lipid storage disorders. Advances in molecular genetics and brain imaging are further augmenting clinicians' insights to diagnose and to guide therapy.
Progress is gaining momentum, with an unprecedented variety of new treatment and prevention strategies under development: drugs to home in on the molecules that cause disease, stem cell therapies to replace lost nerve cells, neural prostheses to read control signals directly from the brain, immune tolerance approaches to prevent stroke, therapies to repair or replace defective genes, and behavioral interventions to encourage the latent "plasticity" of the brain and spinal cord toward self-repair. Each of these strategies relies upon remarkable advances in understanding how the normal nervous system works and what goes wrong in disease.
A few findings from the past year illustrate this progress: Scientists studying genes discovered a mutation that causes a form of Charcot-Marie-Tooth disorder, a common disabling disease of peripheral nerves; pinpointed the site of a gene contributing to autism; and found clues about how a chromosome defect causes facioscapulohumeral dystrophy, a common form of muscular dystrophy. In animal models of human disease, themselves often the product of gene research, gene therapies have yielded encouraging results for neurofibromatosis, Fabry disease and Parkinson's. Scientists on the trail of cell therapies discovered that primitive precursor cells in the adult rat brain can respond to experimental damage by multiplying, migrating to the site of damage, and making new nerve cells, and that transplanted embryonic stem cells show promise in animal models of Parkinson's disease, stroke, and other disorders. Scientists focusing on the immune system found that a strategy, which suppresses immune reactions, prevents strokes in hypertensive rats; that an anti-cholesterol drug, the statin Lipitor, reduces symptoms in an animal model of multiple sclerosis; and that the gene defect in Batten disease may result in unexpected immune reactions, which could contribute to the devastating consequences in the brain. In research on drug treatments, the antibiotic minocycline slowed progression of amyotrophic lateral sclerosis in mice; the natural brain chemical inosine stimulated rewiring of the brain following stroke in rats; and coenzyme Q10 may slow progression of Parkinson's disease. Scientists studying new technologies developed a device that enabled rats to control a robot arm just by thinking about it; devised better ways to delivery therapeutic agents to the brain; used microarrays to monitor the activity of thousands of genes, yielding insights about brain tumors and multiple sclerosis; and for the first time, recorded activity of the human fetal brain in response to light, which may lead to better prenatal diagnostics.
NINDS continues to rely on the insight and ingenuity of scientists and physicians throughout the nation to seek out scientific opportunities, propose research studies, and advise on promising ideas. Since Congress began the NIH budget doubling effort, the Institute has taken a more active role in directing research. Efforts are motivated by scientific opportunity, enabled by resources, guided by extensive and inclusive planning efforts, and quality-assured through peer review. Programs target specific diseases and cross-cutting opportunities to enhance the effectiveness of research. A few examples illustrate the wide range of activities:
The NIH Parkinson's Disease Research Agenda is the pacesetter for disease-focused NINDS activities. The Agenda began in January 2000 with a working group that included Parkinson's disease researchers, patient advocates, industry representatives, and NIH scientific staff. Follow-up meetings, most recently a July 2002 "summit" called by the NIH Director, have updated priorities to reflect the changing scientific landscape and to address roadblocks to progress. Since March 2000, the Parkinson's effort has included more than 20 solicitations, more than a dozen workshops, establishment of a network of Morris K. Udall Centers, major clinical trials, and funding of the Deep Brain Stimulation Consortium. The NINDS Office of Minority and Health Research is also leading a major effort to implement the NINDS Five Year Strategic Plan on Minority Health Disparities, and developing goals specific to neuroAIDS, stroke and epilepsy. Implementation of planning efforts in brain tumor, stroke, and epilepsy are also under way. Other initiatives are focusing on diseases such as autism, muscular dystrophy, and spinal muscular atrophy, and NINDS continues to support a variety of disease-focused scientific workshops to assess current understanding, stimulate research interest, and foster collaborations.
Re-engineering the research enterprise: NINDS has designed and conducted pioneering clinical trials to test the safety and effectiveness of interventions to prevent and treat neurological disorders. In recent years, the Institute augmented clinical trials activities with new grant mechanisms for planning trials and for pilot trials; developed procedures and increased professional staff to optimize trial design and monitoring; and created a subcommittee of the NANDS Council to provide broad advice on priorities for clinical research, including trials. This year, NINDS is beginning to supplement ongoing clinical trials to capture genetic samples for a newly established DNA and cell line repository. For the future, the Institute is exploring options to create a network of physician-investigators to carry out clinical trials. Such a program might speed trials, minimize costs, enhance accessibility for patients, facilitate the recruitment of a diverse spectrum of participants, improve feasibility of trials for rare diseases, and accelerate the transfer of results to practice in community settings.
A highlight of the clinical trials program is an innovative trial of neuroprotective drugs for Parkinson's disease, that is, drugs which slow disease progression rather than just temporarily improving symptoms. The Institute reached out widely to academia and industry, here and abroad, for suggestions of possible drugs, and developed a rigorous evaluation process, which has selected the most promising drug candidates. A network of more than 40 clinical sites, with central statistical and data coordination, has been established to carry out the trial. NINDS is working closely with voluntary groups to recruit patients. The first pilot studies may begin this spring.
Translational research is another major focus of cross-cutting efforts. NINDS has a long history of translational research, which moves fundamental discoveries about the brain and disease toward therapies and clinical trials. Advances in neuroscience are yielding increasing opportunities for translation, and NINDS responded in July 2002 by launching a comprehensive program to foster translational research. Essential to this program are peer review criteria tailored to the needs of translational research, milestone driven funding, and training a cadre of investigators to carry out translational research. The goal is to provide an environment where coalitions of basic scientists and clinicians can design and carry out preclinical studies required to bring therapeutic candidates to the point where clinical studies can begin.
New pathways to discovery: Several NINDS programs are exploring new avenues for discovery. NINDS has established a goal of identifying small molecules that are active in the nervous system and show promise as therapeutic candidates, diagnostic agents, or research tools. In 2002, the Institute established a consortium to test more than 1000 drugs, most previously approved by the U.S. Food and Drug Administration (FDA) for other conditions, against 29 rapid laboratory assays (tests) related to neurodegenerative diseases. The best candidate chemicals are moving to further testing in animal models through an NINDS supplement program. NINDS has also awarded a contract for a high throughput screening (HTS) center, and is soliciting proposals for the development of assays for HTS. HTS rapidly tests thousands of chemicals to find lead compounds for drug development. In another effort, a contract-based approach to therapeutics development for spinal muscular atrophy will test a new model that might apply to other diseases. The NIH Molecular Library Roadmap Project will speed the discovery process for drugs and chemical research tools by providing access to information databases and to potentially useful compounds. The Institute has also established a facility to provide researchers access to microarray technology, which allows simultaneous monitoring of the activity of thousands of genes in health and disease. Stem cell research remains a high priority for the Institute. NINDS has provided supplements for grantees to pursue stem cell research, and joined with other components of NIH in stimulating this research and targeting aspects critical for the nervous system. An NINDS intramural investigator will lead a new NIH facility to characterize the available approved lines of human embryonic stem cells.
Research teams of the future: Increasingly, progress against neurological disorders requires cooperation among multi-disciplinary teams of investigators. NINDS is enhancing the opportunities for team approaches with general programs to support common resources and specific initiatives tailored to areas such as Parkinson's disease, stroke, autism, muscular dystrophy, spinal cord injury and health disparities. The Institute is also addressing critical training needs in areas such as translational and clinical research. In the NIH Intramural program, the John Edward Porter Neuroscience Center will bring together scientists from ten NIH components that focus on the brain.
Neurological disorders have always challenged the best efforts of medicine. The intricacy of the brain is awesome, its workings are elusive, and an extraordinary variety of disorders affect the nervous system. Furthermore, the brain and spinal cord are difficult to access, sensitive to intervention, and reluctant to regenerate following damage. However, building on advances in basic science, progress is improving peoples' lives, and prospects for the future are even more encouraging. We are working to engage the best minds in the nation and provide them with the resources they need to devise ways to prevent, treat, or, ultimately, cure neurological disorders. Thank you.
Last Modified February 3, 2011