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 Story Landis, Director of the National Institute of Neurological Disorders and Stroke (NINDS). I am pleased to present the Fiscal Year 2007 President's budget request for NINDS.
The mission of the NINDS is to reduce the burden of neurological disorders by developing ways to prevent or to treat these diseases. Epilepsy, autism, cerebral palsy, muscular dystrophy, spinal muscular atrophy (SMA), and hundreds of other disorders are first evident in infancy or childhood. Multiple sclerosis, spinal cord injury, migraine, and traumatic brain injury are among the many nervous system diseases that are prevalent in young adults. Stroke, dementias, chronic pain, and Parkinson's disease will increase, if unchecked, with the aging of our population. The impact of neurological disorders on people, on their families, and on our economy is immense.
The NINDS currently supports more than 1000 clinical research projects, of which more than 125 are clinical trials of interventions to prevent or treat disease. Ongoing clinical trials are testing drugs, natural biological molecules, surgery, deep brain stimulation, hypothermia, radiation, immunotherapy, and behavioral therapies for disorders including amyotrophic lateral sclerosis (ALS), brain tumor, cerebral palsy, epilepsy, headache, Huntington's disease, multiple sclerosis, muscular dystrophy, myasthenia gravis, pain, Parkinson's disease, spinal muscular atrophy, stroke, Tourette syndrome, and traumatic brain injury.
Last year an NINDS clinical trial showed that aspirin prevents stroke effectively for the many people with partially blocked arteries in the brain who have had a previous stroke or TIA (mini stroke). Aspirin works as well as warfarin, a drug that requires monthly monitoring and carries the risk of major hemorrhage and heart attack. This trial is another step in a long march of advances that guide physicians in preventing stroke in particular risk groups. The U.S. Centers for Disease Control and Prevention estimated that the death rate from stroke declined by 18.5% for the U.S. population from 1993 to 2003, and progress is continuing with results like these.
Each year also brings results from several NINDS preliminary clinical trials. Current drugs for Parkinson's disease ultimately fail because they do not halt the progressive death of brain cells that causes this disease. The Neuroprotection Exploratory Trials in Parkinson's Disease (NET-PD) is a network of 50 clinical centers throughout the U.S. that efficiently tests drugs to slow the underlying disease. NET-PD has completed phase II trials of four drugs that had been rigorously selected for testing from candidates suggested by scientists around the world, and just published the results of the first two. Net-PD will move quickly to a large, definitive clinical trial to test the safety and effectiveness of at least one of these drugs in preventing Parkinson's disease.
In addition to clinical trials, other types of clinical studies lead to new treatment or prevention strategies. An epidemiological study this year found that men who exercised vigorously as young adults had a 50% lower risk of developing Parkinson's disease in later life than men who had low levels of physical activity. Other studies determined how to predict which patients with glioblastoma, a common and deadly brain tumor, will respond to a new class of anti-cancer drugs, and discovered why infant seizures do not respond to drugs that are effective in adults and what other drugs might work better.
The NINDS Clinical Research Collaboration (CRC), now under development, will extend the reach of clinical research into more communities across the U.S. The CRC engages community practice and academic neurologists to speed clinical studies; minimize costs; make clinical trials more accessible to diverse participants; facilitate trials of rare diseases; and improve transfer of research results to clinical practice in the community. Complementing the CRC, the NINDS is building a network to develop emergency treatments for neurological disorders. Stroke, seizures, traumatic brain and spinal cord injury, and other neurological disorders account for perhaps 5 to 10 % of all medical emergencies. This program brings together specialists in emergency medicine, neurological disease and clinical trials.
Genes and Neurological Disorders
In December, the journal Science chose the discovery of a gene defect that can cause Tourette syndrome as one of the 10 most important scientific advances of the year. Since the NIH budget doubling began, scientists have identified more than 100 genes associated with neurological diseases including ALS, ataxias, Batten disease, dyslexia, dystonia, epilepsy, muscular dystrophies, Parkinson's disease, peripheral nerve diseases, and spinal muscular atrophies.
Gene discoveries often have a rapid impact on patients and families. They yield definitive DNA diagnostic tests that are faster, cheaper, and more accurate, and allow genetic counseling and attention to special risks of people with particular inherited disorders. For example, patients with ataxia used to undergo MRI brain scans, withdrawal of spinal fluid for analysis, tests for amino acids and organic acids, lipoprotein electrophoresis, urine heavy metal screens, thyroid function tests, and sometimes painful nerve or muscle biopsies to get a diagnosis, costing thousands of dollars over several months. Today, a commercially available DNA test can often give a definitive diagnosis of a genetic neurological disorder within a week for a few hundred dollars.
Gene findings also jump-start therapy development. Over the last year, studies of therapies in animal models, another benefit from gene discoveries, have shown promise for neurofibromatosis, muscular dystrophy, fragile x syndrome, Huntington's disease, hereditary ataxias, and several other disorders. Therapies are already moving from animal models into NIH or private sector clinical trials, including ceftriaxone for ALS, anti-oxidants for ataxia-telangiectasia, myostain inhibitors and gentamicin for muscular dystrophy, and coenzyme Q10 for Huntington's disease. The pace is remarkable after decades without progress for many of these diseases.
Knowing where and when genes are active is key to understanding the nervous system in health and disease. Most genes are active at some time and place in the brain, yet only a small fraction of these have been well characterized, so the NINDS initiated the GENSAT (Gene Expression Nervous System Atlas) to map gene activity in the brain across development. GENSAT also generates valuable research tools including strains of mice in which a visible marker is turned on where and when the gene of interest is active. Using these mice, scientists this year found new insights into Parkinson's disease that could not have been revealed without this resource. The studies showed that one of two previously undistinguishable types of nerve cells is selectively affected in Parkinson's disease, helped explain why brain movement control circuits malfunction, revealed the molecular mechanism that kills those cells, and identified a potential new target for drugs to slow Parkinson's disease.
With the budget increases, the NINDS implemented major programs to move insights from basic research to practical therapies ready for testing in clinical trials, that is, translational research. The Cooperative Program for Translational Research supports research teams in academia and small companies. These milestone-driven, investigator-initiated projects are developing drug, stem cell, or gene therapies for Batten disease, Parkinson's disease, Huntington's disease, tuberous sclerosis, Duchenne muscular dystrophy, traumatic brain injury, and stroke, among other disorders.
In another translational effort, the NINDS developed the SMA Project as a model program to expedite therapy development. The contract-based project is making encouraging progress towards its ambitious goal--having a drug for SMA ready for clinical trials by the end of 2007. A steering committee, with drug development expertise from industry, the FDA, academia, and the NIH, first developed a detailed drug development plan. To carry out the plan, the project then created a virtual drug development company with the tools and facilities for identifying "lead compounds," chemically modifying leads into potentially improved compounds, testing drug candidates in cell and animal models, and coordinating the overall drug development scheme. More than 300 compounds have been prepared and are in testing. In 2007, the NINDS will address a major barrier in the development of drugs for other neurological diseases by extending the contract-based medicinal chemistry resource from the SMA Project. Medicinal chemists modify weakly active compounds so that drug development teams can test the new drugs for improved safety and effectiveness.
NIH basic science stimulates therapy development in the private sector, as well as by the NIH. In the past year, private sector clinical studies of clotting Factors VII and VIIa have shown promise for serious and hard to treat strokes caused by bleeding in the brain. NIH research motivated those studies by showing that these strokes are followed by continued expansion of blood filled pockets in the brain, called hematomas, which contribute profoundly to disability and death. Private sector clinical trials in gene and cell therapies for Parkinson's disease begun this year also build upon NINDS research.
Longstanding NINDS targeted therapy development programs also catalyze private sector efforts. For three decades, the Anticonvulsant Screening Program (ASP) has fostered industry development of drugs for epilepsy, including six drugs in widespread use and several more now in clinical testing. Drugs that emerged from the ASP testing program are also among the most effective treatments for chronic pain. NINDS initiatives begun last year and to begin in 2007 focus on animal models for testing drugs that block the development of epilepsy, work for treatment resistant epilepsy, and meet the special needs of pediatric and geriatric populations.
The NINDS strongly encourages cooperative efforts among scientists and physicians from diverse disciplines, and works closely with other parts of the NIH, other government agencies, and non-governmental organizations, as well as with companies.
As may be evident from the discussions of the Clinical Research Consortium, NET-PD, GENSAT, the Cooperative Program in Translational Research, and the SMA Project, most NINDS programs, whether focused on a particular disease or a scientific problem, emphasize collaboration. Other examples include research centers on muscular dystrophy, Parkinson's, autism, spinal cord injury, stroke and heath disparities, and resources including the Human Genetics Repository and the Microarray Consortium.
The NIH Neurosciences Blueprint, begun in 2005, presents a framework to enhance cooperation across the NIH institutes that share an interest in diseases of the nervous system. Blueprint initiatives have focused on neuroscience tools, training in the neurobiology of disease for basic scientists, genome analysis, neuroimaging, genetic mouse models, core research facilities, and clinical assessment tools. In 2007, the Blueprint will focus on neurodegeneration, which contributes to many diseases.
Among government agencies, the NINDS is working closely with the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) because many potential chemical terrorist agents affect the nervous system. Cooperative projects with the Veterans Administration include a major clinical trial of deep brain stimulation for Parkinson's disease. The NINDS also meets regularly with the FDA on stem cells and other biological therapies and works with the National Science Foundation on common interests including computational neuroscience and informatics.
More than 300 non-governmental organizations (NGOs) focus on diseases within the mission of the NINDS. The World Parkinson Conference, held for the first time this February, and a major conference on epilepsy planned for March 2007 are two of many recent examples of cooperative efforts between NGOs and the NINDS. In June 2005, the Institute brought together 75 representatives of NGOs at the NIH for a day of presentations, informal interaction, and group discussions. Based on the strong positive feedback from participants, the NINDS will hold similar meetings in the future to explore how we can work together in the future.
Thank you, Mr. Chairman. I would be pleased answer questions from the Committee.
Last Modified March 14, 2012