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underway to evaluate whether longer treatment with methylprednisolone or the use of a different steroid may provide even greater benefit. This year, NINDS is establishing a pilot program of regional clinical research centers for head and spinal cord injury. These centers will develop improved therapies, promote research on restoration and preservation of function after injury, and provide the environment necessary for the recruitment and training of investigators for research on central nervous system trauma. regional centers will add an important dimension to the NINDS research effort in 1992 to improve the outcome for many of the estimated 10,000 Americans who will have a spinal cord injury and the 500,000 who will experience a headinjury.
NINDS scientists and grantees are pursuing other avenues to "tease out" the various chemical and cellular events triggered by injury to the nervous system and devise methods to block or enhance nerve cell activity for therapeutic effect. For instance, in stroke patients, damaged nerve cells can spill out dangerous levels of excitatory amino acids and produce toxic supercharged molecules of oxygen known as free radicals, The next step is to evaluate promising agents to neutralize these chemicals and prevent the progression of stroke. Research studies are also defining the role of free radicals in Parkinson's disease and also the damaging interaction between free radicals and blood vessels in the brain that can result from seizures. Investigators are pursuing recent evidence that suggests the same mechanism to secrete excitotoxins may be at work in head injury and neuro-AIDS. Greater attention can now be given to study of the selective
vulnerability and degeneration of nerve cell populations. Our Institute's research objective is to prevent brain cell degeneration or arrest it in the very earliest stage of diseases such as Alzheimer's disease and Parkinson's disease. ́Aged, nonhuman primates are an important research model for Alzheimer's disease, helping to elucidate the development of nerve cell abnormalities and the deposition of amyloid protein in the plaques characteristic of this disease. New genetic studies, neurochemical studies, and the development of advanced imaging methodologies are being emphasized to shed more light on the fundamental cause of Alzheimer's disease. The long term effects of deprenyl and the value of tocopherol--a component of vitamin
E--in combination with deprenyl to treat people with Parkinson's disease are being evaluated in an ongoing clinical trial. Study of tissues from people with amyotrophic lateral sclerosis, or Lou Gehrig's disease, has provided a lead to evaluate the use of branched-chain amino acids for this disease.
One third of the people who will have a stroke this year will become permanently disabled: stroke is the most common cause of disability requiring rehabilitation. The NINDS research effort on stroke will be enriched by a newly established intramural program. We also have ongoing clinical trials to evaluate clot-dissolving agents--tPA and heparinoids--for their effectiveness in limiting brain damage from ischemic stroke. We are working with a time-frame of only 90 minutes to three hours to determine whether tPA must be given as an emergency measure in order to be effective. Studies are also underway to elucidate risk factors and prevent stroke in those people at risk for an initial insult or recurrence. Within the past year, the NINDS found that aspirin and warfarin were so effective in preventing stroke in people with atrial fibrillation that as many as 30,000 people could be spared from a stroke this year, at a potential health care savings of $200 million. Early results from another, ongoing study have related ethnic differences in risk factors to differences in stroke type and outcome. NINDS has revised and reissued a program announcement to encourage new studies in Blacks, other minorities, and women to improve our understanding of different risk factors and types of stroke in various populations. ར ར : ¥
Intramural scientists using magnetic resonance imaging (MRI) have evidence that multiple sclerosis (MS) progressively attacks the central nervous system even when patients may be relatively symptom-free. This finding will change the way many patients are treated, especially in the early stages of the disease. In other work, intramural and extramural investigators are deciphering the immunologic processes related to MS and exploring new forms of treatment such as the possibility of a T-cell vaccine. At a minimum, 25 percent of all genetic disorders affect the brain and rervous system, some estimate that there are neurological consequences in
70 percent of all genetic disorders. Neurogenetics research is brimming with a proportional number of research opportunities. The chromosomal bases for 19 neurological or neuromuscular disorders are now known. The
neurofibromatosis 1 (NF-1) gene has been located on chromosome 17; ongoing research will clarify the gene's normal function and its role in the symptoms of NF-1 and other disorders of cell growth such as cancer. closing in on the genetic basis of some forms of epilepsy. Intramural investigators are refining the optimal dose for enzyme replacement therapy in Type 1 Gaucher's disease while continuing the development of methods to repair or replace the defective gene. Dystrophin research has unexpectedly revealed that other genes may be producing proteins that can "pinch hit" for dystrophin and mitigate the symptoms of muscular dystrophy. Both genetic linkage studies and studies of cell biochemistry are probing independently the underlying causes of the various types of Batten's disease. In other studies, researchers are working to isolate and sequence the gene for the animal model of narcolepsy. While investigators continue work to localize the genetic defect in Huntington's disease (HD), research to determine the physiologic defect and possible therapies has progressed; preliminary efforts are underway to test the efficacy of a drug called idebenone to protect atrisk brain cells. Transgenic mice are also being developed as a genetic model for HD--an invaluable tool for the expected wave of new studies once the gene is found.
An estimated 10 to 15 percent of all children have mild cognitive deficits or learning disabilities. This year, an estimated 9,000 babies will develop cerebral palsy and several thousand more babies and children will have to live with--or die from--the neurological consequences of their mother's drug abuse. An ongoing multidisciplinary study to develop, standardize, and validate a uniform classification system for the diagnosis of children with higher cortical dysfunctions will facilitate research. Improved treatments for epilepsy in the pediatric age group are a priority for the Institute.
As evidenced by the advances and initiatives described here, we cannot separate progress in prevention, treatment, and diagnosis from the importance of basic neuroscience research. Neurochemistry and neurobiology are providing important leads to understand cognition and behavior. NINDS grantees recently found that one possible mechanism for strengthening long term neural interactions appears to be the ability of the sending cell in
"memory centers" to release more neurotransmitter.
Studies of single nerve
cell activity are feeding into better understanding of brain circuits activated by normal cognitive functions or affected by disease.
Brain imaging technology continues to push back the limits of our ability to study the living brain. Experiments with positron-emission tomography (PET) have linked discrete areas of the brain to word-processing tasks and have confirmed the unique role PET has for understanding the higher cognitive functions. New PET tracer chemicals are opening the door to view
the working circuitry of the brain. MRI has been established as a critical · tool for research on neuro-AIDS and multiple sclerosis (MS); new studies will further elaborate understanding of how MS attacks the nervous system and will be very important in evaluating the effectiveness of treatments. The application of several techniques to the same research problem is proving very fruitful; PET, MRI, and magnetoencephalography (MEG) provide complementary information necessary to precisely diagnose and localize the epileptic focus--especially critical when considering surgery. Ongoing research seeks to overcome technological barriers to better integrate data from PET and MRI. These exciting opportunities underscore the importance of brain imaging centers in which these technologies could be integrated and applied to brain research.
Exciting work with neural prostheses points the way to restoration of function in the damaged nervous system. A neural prosthesis that will utilize extension movement in the wrist to control opening and closing of the hand is under development. A brain probe containing both electrodes and cultured neurons is being developed to make very specific connections with the central nervous system. Scientists are also studying genes called into action after traumatic injury to the nervous system for their potential to promote nerve cell growth and regeneration.
The declaration of the 1990s as the Decade of the Brain has generated new enthusiasm among neuroscientists, stimulated international collaborative research efforts, and provided a focus for efforts to highlight and maintain the U.S. lead in research, medicine, and biotechnology. The promise of the "Decade" has provided in its first year new treatments benefiting many
Americans--treatments which in many cases have the added plus of being
inexpensive or cost-saving. The potential for further progress, as outlined in the "NINDS Implementation Plan for the Decade of the Brain," impacts particularly vulnerable segments of our population--elderly, children, and minorities--and encompasses many of the major health care problems facing the nation today, such as AIDS and drug abuse. Significant progress has been achieved in the neurosciences in just the past few years. We are optimistic that in the year 2000, when we look back to see what has been accomplished in the "Decade of the Brain", we will be pleased with the progress made in understanding the human brain and significantly improving the quality of
Mr. Chairman, the FY 1992 budget request for this Institute is $583,355,000. I am pleased to answer any questions you might have.
BIOGRAPHICAL SKETCH OF DR. MURRAY GOLDSTEIN
October 13, 1925, New York, New York
EDUCATION: B.A., New York University, 1947; D.O., Des Moines Still College of Osteopathic Medicine, 1950; M.P.H., University of California, School of Public Health, 1959; Mayo Clinic (Neurology), 1968.
PROFESSIONAL HISTORY: Director, NINDS, 1982-present; Acting Director,
PROFESSIONAL ORGANIZATIONS: American Academy of Neurology; American Association for the Advancement of Science; American Heart Association, Council on Stroke; American Neurological Association; American Osteopathic Association; Member, Board of Directors, John P. Robarts Research Institute, London, Ontario, Canada; Society for Neuroscience; The American Parkinson Disease Association, Medical Advisory Board; United Cerebral Palsy Research & Educational Foundation, Board of Directors; Consultant (Neurology), Pan American Health Organization; Consultant, World Health Organization Program on Neurosciences; Chairman, World Health Organization Task Force on Cerebrovascular Disorders; Commission on Alternative Health Care, U.S. Olympic Council on Sports Medicine; Councilor, Neurotrauma Society; Board of Directors, National Stroke Association.
HONORS AWARDS: Beta Alpha Epsilon, Biology National Honor Society, NYU; Psi Chi, Psychology National Honor Society, NYU; Sigma Alpha, Osteopathic Scholarship National Honor Society, College of Osteopathic Medicine; Delta