Senate Subcommittee on Labor-HHS-Education Appropriations
Statement by Story C. Landis, Ph.D.
Director, National Institute of Neurological Disorders and Stroke
Mr. Chairman and Members of the Committee:
I am pleased to present the Fiscal Year 2012 President's budget request for NINDS. The Fiscal Year (FY) 2012 budget is $1,664,253,000. Our mission is to reduce the burden of neurological disorders through research. NINDS research has improved diagnosis, prevention, and treatment, but the best of medical science is still far from optimal for most nervous system disorders. Fortunately, advances in understanding the brain and its disorders are providing extraordinary opportunities for progress.
Enhancing the Evidence Base for Medical Decisions
U.S. Centers for Disease Control and Prevention statistics show that from 1997 to 2007 the stroke death rate in the U.S. decreased 34.3%, and the number of stroke deaths declined 18.8%, which translates to thousands of lives saved and thousands with reduced disability every year. For decades, NINDS clinical trials have contributed to this trend by providing evidence that enables physicians to choose the best stroke prevention interventions according to each person’s risk factors. In April, NINDS stopped a stroke prevention clinical trial early because the results were already clear1. The trial included patients at high risk because of a prior non-disabling stroke and severe narrowing of arteries to the brain. Angioplasty combined with stenting, which opens clogged arteries with a tiny balloon and inserts a device to prop them open, plus aggressive medical therapy led to a higher risk of stroke than the medical therapy alone. Another recent NINDS clinical trial showed that a procedure using stents is as safe and effective in preventing stroke as carotid endartarectomy, a more invasive surgical procedure to clear arteries, in people with certain risk factors 2. Follow up to monitor longer term results is continuing for both trials. NINDS clinical trials are similarly guiding treatment for other diseases. A recent clinical trial showed that an older drug, ethosuximide, may be the best first drug to test to prevent seizures with minimum side effects in children with absence epilepsy, providing much needed guidance for treating this common disorder 3. An NINDS-Department of Veterans’ Affairs trial showed that surgical implantation of deep brain stimulators (DBS) can yield better movement and quality of life than drug treatment for people with advanced Parkinson’s disease, and more recent results of this trial provided information about choosing the best site in the brain to implant electrodes for each patient 4. NINDS currently supports 32 multi-site clinical trials to test the safety and effectiveness of interventions in stroke, epilepsy, traumatic brain injury, multiple sclerosis, muscular dystrophy, and other diseases, and more than 120 earlier phase trials that are essential steps toward large efficacy trials.
Advancing Translational Science
Since long before the term “translational” became common, NINDS has pushed development of basic science advances into drug, biologic, and device therapies. The first enzyme therapy for inherited metabolic diseases, several drugs for epilepsy, the first emergency treatment for stroke, and pioneering technology for devices that replace lost nervous system function are among advances that NINDS translational research made possible. Often, industry capitalizes on NIH basic science findings to develop a new therapy. However, rare diseases, bold new therapeutic strategies, and new uses for existing drugs are all challenges that NINDS is more likely than industry to take on. This is especially so now because drug companies, citing the extraordinary challenges of brain research, are reducing programs to develop nervous system drugs 5.
NINDS launched the Cooperative Program in Translational Research in 2003 to exploit increasing opportunities from neuroscience research. This program supports teams of academic and small business investigators to carry out milestone-driven, preclinical therapy development for a broad range of neurological disorders. The first candidate therapies from this program have moved into clinical testing for disorders including stroke, Batten disease, and muscular dystrophy.
Several NINDS programs meet special translational needs for particular diseases. Among these are the Anticonvulsant Screening Program, the Specialized Centers of Translational Research in Stroke (SPOTRIAS), the Udall Centers of Excellence in Parkinson’s disease, and the Wellstone Centers for Muscular Dystrophy Research. NINDS chose spinal muscular atrophy (SMA) as the disease to pilot another innovative approach to drug development. With experts from academia, industry, and FDA, the SMA Project designed a drug development plan and is implementing the plan through a “virtual pharma” organization that engages resources via contracts. Promising drug candidates are now in advanced pre-clinical testing, and the Project is working toward certification for a clinical trial in 2012. Building on the SMA Project strategy, NINDS is leading the NIH Blueprint for Neuroscience in a larger scale Grand Challenge on Neurotherapeutics. The challenge goal is to develop truly novel drugs that will transform the treatment of nervous system diseases. The NINDS Intramural Research Program, which has a long record of therapy development, is also accelerating translational research under a new Clinical Director. NINDS translational programs work closely with all of the NIH-wide programs and resources that will become part of the National Center for Advancing Translational Sciences (NCATS), and will certainly benefit from NCATS programs to catalyze translational research.
Because novel therapies for several neurological diseases are moving toward readiness for clinical testing, NINDS is developing a multi-site clinical network to improve the speed and effectiveness of the early steps in clinical testing of novel therapies for neurological disorders. Better early phase testing will increase the likelihood of success in larger and more expensive phase III clinical trials of effectiveness. This network will test promising interventions, whether they arise from academia, foundations, or industry, and will engage expertise much greater than the Institute could dedicate to separate networks for each of the many neurological diseases. This is especially important for rare disorders, including pediatric diseases. A project to validate biomarkers for SMA will be among the network’s first studies.
Another major clinical initiative will develop and validate biomarkers for Parkinson’s disease, that is, measurable indicators of the disease process. Biomarkers research, which NINDS supports for many disorders, exemplifies another way that NINDS programs can catalyze both NIH and industry therapy development efforts. With biomarkers for neurodegenerative disorders, clinical trials can determine in months, rather than years, whether drugs are slowing the progression of disease and understand why a new treatment worked or did not. Better biomarkers can reduce the cost of research and speed the development of better treatments in NIH and industry.
Accelerating Progress through Technology
An extraordinary array of technologies has accelerated progress in neuroscience. These range in scale from imaging activity of the thinking human brain as people carry out complex tasks, to understanding atom by atom how molecules control electrical activity in brain cells. This year research demonstrated the power of whole genome sequencing to understand Charcot-Marie-Tooth disorder, a peripheral nerve disease 6. This is a harbinger of personalized genomics for many diseases. Next generation genomics research is underway for several neurological disorders. A “Center without Walls” will bring together the best possible team, regardless of geography, to apply advanced genomics to epilepsy. On another technological frontier, ARRA enabled NINDS to accelerate research on induced pluripotent stem cells (iPSC’s) that can be derived from patients with Parkinson’s, Huntington’s, ALS, epilepsy, and other disorders. A spate of new technologies, from methods that label nerve cells with more than a hundred different colors, to computerized 3-dimensional reconstruction of intricate nerve cell circuits, to techniques that control the activity of individual nerve cells with light, are arming neuroscientists to meet the longstanding challenge of understanding how circuits of nerve cells underlie memory, perception, complex movement, and other higher brain functions. This has implications for understanding autism, epilepsy, Parkinson’s, Alzheimer’s, and many other diseases.
Encouraging New Investigators and New Ideas
When progress against disease is not forthcoming, a gap in basic understanding of the normal brain or the disease process is often the cause. Physicians and scientists across academia and industry agree that basic research propels long-term progress against disease. The insight and ingenuity of the research community is the key. Supporting a vigorous scientific community and investigator-initiated research are thus high priorities throughout NINDS programs and policies. To encourage innovative research, for example, the EUREKA (Exceptional Unconventional Research Enabling Knowledge Acceleration) program complements the NIH Pioneer Awards, New Innovator Awards, and Transformative R01’s, all of which support neuroscientists. To prepare the next generation of neuroscientists, NINDS training and career development programs are tailored to the needs of basic and clinical researchers, and funding policies favor early stage investigators. NINDS encourages cooperative research and promotes sharing through several programs. Examples include the Common Data Elements program, Human Genetics Resource Center, consortia on induced pluripotent stem cells, disease centers programs, and other grants to multi-investigator teams. NINDS is improving programs on workforce diversity and health disparities based on guidance from an external review and planning process that was completed in 2011.
Neurological disorders present formidable challenges. Nonetheless, prospects for progress have never been more encouraging because of progress in understanding the nervous system and its diseases at every level from molecules through the working human brain. NINDS is aggressively pursuing better prevention and treatment with a balance of basic, translational, and clinical research, supported through investigator-initiated and priority-targeted programs.
2 Brott TG et al. Stenting Compared to Endarterectomy for Treatment of Carotid Artery Stenosis, New England Journal of Medicine 363:11-23 2010
3 Glauser et al. Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy. New England Journal of Medicine. 362:790-799 2010
4 Weaver F. et al. Best Medical Therapy versus Bilateral Deep Brain Stimulation for Patients with Advanced Parkinson’s Disease: A Randomized Controlled Trial. JAMA 301:63-73 2009; Follett et al. Pallidal versus Subthalamic Deep Brain Stimulation for Parkinson’s Disease. New England Journal of Medicine 362:2077-91 2010
5 "R&D Cuts Curb Brain-Drug Pipeline," The Wall Street Jounal, March 27, 2011
6 Lupski JR et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. New England Journal of Medicine 362:1181-91 2010
Department of Health and Human Services
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Story C. Landis, Ph.D.
Dr. Story C. Landis began her appointment as the Director of the National Institute of Neurological Disorders and Stroke (NINDS) on September 1, 2003. A native of New England, Dr. Landis was awarded her B.A. degree in Biology, with highest honors, from Wellesley College (1967), and her M.A. (1970) and Ph.D. (1973) degrees from Harvard University. After postdoctoral work at Harvard University studying transmitter plasticity in sympathetic neurons, she served on the faculty of the Harvard Medical School’s Department of Neurobiology.
In 1985, Dr. Landis joined the faculty of the Case Western Reserve University School (CWRU) of Medicine in Cleveland, Ohio, where she held many academic positions, including Associate Professor of Pharmacology, Professor and Director of the Center on Neurosciences, and Professor and Chairman of the Department of Neurosciences, a department that she was instrumental in establishing. Under her leadership, the CWRU Department of Neurosciences achieved worldwide acclaim and a reputation for excellence. In 1995, Dr. Landis was appointed as the NINDS Scientific Director, and was responsible for the direction and re-engineering of the Institute’s intramural research program. Beginning in 1999, in conjunction with the leadership of the National Institute of Mental Health (NIMH), she spearheaded a movement to bring a sense of unity and common purpose to the numerous laboratories, in multiple NIH Institutes, that conduct leading edge clinical and basic neuroscience research, which increased research cooperation and collaboration, and resulted in the construction of the new NIH Neuroscience Research Center, Phase II of which is currently under construction on the NIH campus. Since early 2007, Dr. Landis has also been Chair of the NIH Stem Cell Task Force.
Throughout her research career, Dr. Landis has made many fundamental contributions to understanding the developmental interactions required for synapse formation, and has garnered many honors and awards. Dr. Landis is an elected Fellow of the American Academy of Arts and Sciences and the American Association for the Advancement of Science, and an elected member of the American Neurological Association. In 2002, she was elected President of the Society for Neuroscience, and served as President-elect until her appointment as the NINDS Director in September 2003. In 2009, Dr. Landis was elected to the Institute of Medicine of the National Academy of Sciences.