Fiscal Year 2013 Budget Request (House)

House 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 President’s budget request for the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH). The Fiscal Year 2013 NINDS budget of $1,624,707,000 includes an increase of $278,000 over the comparable FY12 level of $1,624,429,000. The NINDS mission is to reduce the burden of neurological diseases through research. NIH research has improved the lives of many people with neurological disorders directly and by providing the foundation for private sector research. The American Heart Association (AHA) reported that the stroke death rate decreased by 34.8% from 1998 to 2008. Better treatments are available for multiple sclerosis, epilepsy, Parkinson’s, and other diseases, and genetics research has led to tests that significantly reduce the time to obtain the correct diagnosis for many rare disorders. Moreover, basic science is driving remarkable opportunities for progress. Paradoxically, however, industry is significantly reducing their investment in research on brain disorders because of the challenges brain diseases present1. NINDS supports a spectrum of basic, translational, and clinical research to complement and encourage private sector efforts. Because gaps in basic understanding of the normal brain or disease are most often the cause when progress against neurological disease is not forthcoming, the Institute continues to invest more than half of its resources in basic research, for which the NIH role is especially crucial.

Accelerating Discovery

Last year, for the first time, researchers provided a molecular diagnosis for a family’s inherited disease using whole genome sequencing (WGS)2. The disease was a type of Charcot Marie Tooth disease, a disorder that affects the body’s nerves. This year WGS provided not only a molecular diagnosis but also immediate therapeutic benefit3. In this study, twin children had been diagnosed with dopa-responsive dystonia, a movement disorder that reflects a deficiency of the neurotransmitter dopamine. The children’s health problems persisted despite treatment with the drug l-dopa, which replenishes dopamine and is usually effective. Once WGS identified the specific gene defect, it became apparent that the neurotransmitter serotonin was also deficient. Boosting serotonin with a readily available drug dramatically improved the children’s health. Dozens of studies are now underway using these “next generation” sequencing methods in common and rare neurological diseases. A new “Center without Walls,” for example, is bringing the best researchers together, regardless of geography, to apply the new genetics technologies to epilepsy.

Next generation sequencing is just one of several technologies that are transforming basic and clinical neuroscience. Optogenetics allows precise control of nerve cells’ activity by light. Induced pluripotent stem cell (iPSC) methods derive nerve cells from skin cells of patients affected by disease, to enable studies of disease and screening of drugs in a culture dish. NINDS supports extensive iPSC research, including consortia in ALS, Parkinson’s, and Huntington’s disease. Brain imaging now reveals structure, activity, and chemistry of the living brain in health and disease. Recently, for example, brain imaging provided insights about traumatic brain injuries (TBI) in the military, the lingering effects of concussions in young athletes4 and new understanding of autism5. The NIH Human Connectome Project is an ambitious imaging effort to map the wiring diagram of the entire human brain. NIH encourages sharing of data from the Connectome project, gene studies, iPSC methods, and other research that is producing extraordinary amounts of useful information. A notable recent effort to promote data sharing is a TBI database created jointly by the NIH and the Department of Defense6.

Translating Discovery to Health

NINDS has a long history of translating scientific advances into better medicine. Rare disease studies, bold new therapeutic strategies, and technology development are examples of translational research in which NINDS plays a key role. Several NINDS programs support translational research. The Anticonvulsant Screening Program (ASP) has contributed to the development of eight epilepsy drugs now on the market. Following an external review completed this year, the ASP will refocus on what most concerns the epilepsy community today—drugs to address treatment-resistant epilepsy and to modify the course and development of the underlying disease. Recent activities in the NINDS Neural Prosthesis Program, which pioneered this entire field, include collaboration with DARPA (Defense Advanced Research Projects Agency) to enhance brain control of an advanced prosthetic arm, and development of an ultrathin flexible brain implant that could one day be used to treat epileptic seizures and other disorders7. To exploit opportunities across all neurological disorders, the Cooperative Program in Translational Research, begun in 2002, supports teams of academic and small business investigators to carry out preclinical therapy development. NINDS is now funding two Phase II clinical trials of therapies developed in this program. NINDS is also leading an NIH Blueprint Grant Challenge to develop truly novel drugs that will transform the treatment of nervous system diseases.

Because candidate therapies for many disorders are emerging, in 2011 NINDS launched the NeuroNext clinical network at 25 sites across the U.S. NeuroNext will remove roadblocks to the crucial early stage clinical testing of novel therapies and reduce from years to months the time to move new therapies into testing in patients. NeuroNext will test biomarkers for spinal muscular atrophy (SMA) in its first clinical study to prepare for trials of candidate therapies for SMA.

NINDS phase III, multi-center clinical trials continue to advance public health. The Neurological Emergency Treatment Trials (NETT) network completed the Rapid Anticonvulsant Medication Prior to Arrival (RAMPART) trial well ahead of schedule, showing that paramedics in the field can safely deliver the drug midazolam into muscle using an autoinjector (like an EpiPen) and stop continuous seizures faster than the usual intravenous treatment.8 These results inform responses to common continuous seizures and seizures caused by industrial accidents or nerve agents. NETT trials of stroke and TBI emergency treatments are underway. Also this year, the Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMPRISS) clinical trial showed that patients at high risk for a second stroke who received intensive medical treatment had fewer strokes and deaths than patients who received a stent in blood vessels that supply the brain in addition to the medical treatment9. Follow up is continuing to compare longer term benefits.

With the concern about dementia as our population ages, it is worth noting that stroke is a major contributor to dementia, highlighting the complex relationships among various types of dementia. Not only do the 7 million U.S. stroke survivors have an increased likelihood of cognitive problems, and perhaps also 13 million who have had “silent strokes” 10, but also vascular problems that cause stroke are also associated with Alzheimer’s disease. Signs that a stroke has occurred are often found in the brains of Alzheimer’s patients, and beta-amyloid, a key protein in Alzheimer’s pathology, may stimulate the formation of blood clots, which can cause stroke11. Furthermore, last year the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is following more than 30,000 people, reported that high blood pressure and other known risk factors for stroke increase the risk of cognitive problems, even among people who have never had a stroke12. Research suggests that there is a dementia spectrum from pure vascular dementia to pure Alzheimer’s disease, with most patients having contributions from both13. Recognition of intersections not only between Alzheimer’s disease and stroke, but also Alzheimer’s disease with TBI, Parkinson’s, frontotemporal dementia, and other disorders may provide leads toward better prevention and treatment of all dementias.

Hundreds of neurological disorders affect patients, families, and society. The aging population, concern about the long lasting effects of TBI, and reduced private sector investment are among several factors that underscore the importance of NINDS funded research. Although neurological disorders present enormous challenges, progress in neuroscience and other areas of research provides exceptional opportunities for the future.

1 The Wall Street Journal, March 27, 2011; Nature 480:161-2, 2011 (December)
2 New England Journal of Medicine 362:1181-91 2010
3 Science Translational Medicine 3:1-6, 2011
4 NeuroImage 55:1716-27, 2011; Neurology 74:643-650, 2010
7 Nature Neuroscience 14:1599-605, 2011
8 New England Journal of Medicine 366:591-600, 2012
10 Circulation 125:e2-e220, 2012
11 Neuron 66:695-709, 2010
12 Neurology 77:1729, 2011; Annals of Neurology 70:229-36, 2011
13 Neurology 72:368-74,2009

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.