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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

fo: 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. The 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 head

injury.

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 cán spilt 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 Parkiason'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. ' Oui 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

tern effects of deprenyl and the value of tocopherol--a component of vitamin

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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.

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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.

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

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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

nervous system, some estimate that there are neurological consequences in

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70 percent of all genetic disorders. Neurogenetics research is brimming with

à proportional number of research opportunities.

The chromosomal bases for

19 neurological or neuromuscular disorders are now known.

The

neurofibromatosis I (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.

Scientists are

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 Caucher'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

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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 at

risk 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', 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

ack 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

Americang--treatments which in many cases have the added plus of being

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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

life.

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.1., New York University, 1947; D.O., Des Moines still college of Osteopathic Medicine, 1950; M.P.8., University of California, School of Public Health, 1959; Mayo clinic (Neurology), 1968.

PROFESSIONAL BISTORI : Director, NINDS, 1982-present; Acting Director,
NINCDS, 1981-1982; Deputy Director, NINCDS, 1978-1981; Medical Officer,
Commissioned Corps, PAS (Assistant Surgeon General), 1953-present; Director,
Stroke and Trauna Progru, NINCDS, 1976-1978; Director, Extramural Programs,
NINCDS, 1961-1976; Visiting Scientist, Mayo Clinic and Graduate School,
Rochester, Ninnesota, 1967-1968; Chief, Special Projects Branch, NINCDS,
1960-1961; Assistant Chief, Research Grants Reviev Branch, DRG, 1959-1960;
Acting Chief, Section on Virus Diseases of the CHS, Bureau of Acute
Communicable disease, California State Department of Public Health, 1958;
Director, Epidemiology and Biometry Training Grant Program, DRG, 1956-1958;
Assistant Chief, Grants and Training Branch, NBI, 1953-1958; NIH
Representative, DOB Interagency Committee on Bandicapped Resourch, 1982-1990;
Member, DÅBS Task Force on Alzheimer's Disease, 1983-present; Chairman, DHES
Interagency Comittee on Spinal Cord Injury, 1986-1987; Commissioner, DHAS
National Commission on Orphan Diseases, 1986-present; Chairman, DHBS
Interagency Committee on Bead injury, 1988-1989.

PROFESSIONAL ORGANIZATIONS: American Acadeny of Neurology: American
Association for the Advancement of Science; American Heart Association,
Council on Stroke; American Neurological Association; Aner ican 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 Progran
on Neurosciences; Chairman, World Bealth 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 Bonor Society, NYU; Psi chi, Psychology National Honor Society, NYU; Sigma Alpha, Osteopathic Scholarship National Honor Society, College of Osteopathic Medicine; Delta

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