DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

Fiscal Year 2006 Budget Request

Witness appearing before the

House Subcommittee on Labor-HHS-Education Appropriations

Story C. Landis, Ph.D., Director

National Institute of Neurological Disorders and Stroke

March 9, 2005

Number range CHAPTERWilliam Beldon, Deputy Assistant Secretary, Budget

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 2006 President\'s budget request
for NINDS. The FY 2006 budget includes \$1,550,260,000, an increase of
\$10,812,000 over the FY 2005 enacted level of \$1,539,448,000
comparable for transfers proposed in the President\'s request.

The mission of the NINDS is to reduce the burden of neurological
disorders by finding ways to prevent or to treat these diseases. This
mission is extraordinarily important and extraordinarily difficult. It
is important because the burden of neurological disorders is immense,
affecting all segments of society. Diseases of the nervous system kill
people of all ages, disrupt essential bodily functions, cause pain and
discomfort, and disturb all aspects of human ability, from perception
and movement through emotions, memory, language, and thinking. It is
difficult because hundreds of diseases affect the brain, spinal cord,
and nerves of the body, each presenting unique challenges. Compounding
the challenge, the brain and spinal cord are difficult to access,
sensitive to intervention, reluctant to regenerate following damage,
intricate in structure, and elusive in their normal workings.

Despite these challenges, we are making progress. Prevention of stroke
and of nervous system birth defects is having a major impact on public
health. Better drugs and surgical treatments help relieve symptoms for
people with Alzheimer's disease, Parkinson disease, epilepsy, chronic
pain, multiple sclerosis, and other diseases. Improvements in genetic
testing and brain imaging also enhance physicians' ability to diagnose
disease and guide therapy for nervous system disorders.

To continue this progress, the NINDS supports basic studies to
understand the nervous system in health and disease, translational
research to move from the laboratory toward the clinic, and clinical
research, including clinical trials to test the safety and efficacy of
treatments and preventive interventions. The Institute supports most
research through extramural grants and contracts to physicians and
scientists throughout the country. NINDS intramural investigators also
conduct research on the NIH campus in Bethesda, Maryland.

To complement investigator-initiated research, the Institute directs
initiatives to public health needs, unusual scientific opportunities, or
issues that Congress highlights as critical. NINDS initiatives for FY06
focus on tuberous sclerosis, Rett syndrome, muscular dystrophy,
neuro-AIDS, transmissible spongiform encephalopathies (TSEs), stroke,
and Parkinson disease, as well as on cross-cutting issues including
counterterrorism, neurological emergencies, and stem cells.
Increasingly, NINDS initiatives and other programs are in cooperation
with other components of the NIH.

CLINICAL RESEARCH

The NINDS currently supports more than 1000 research projects that
involve human subjects, with more than 300,000 people expected to
participate. For example, epidemiological studies are examining risk
factors for stroke with special attention to Blacks and Hispanics;
genetic studies have recently helped identify genes related to Parkinson
disease, ALS, dystonia, Joubert syndrome, and cerebrovascular disease;
and brain imaging research is revealing how the brain develops
throughout childhood and adapts after damage. Among the findings this
year are brain imaging data that will identify which stroke patients
might benefit from emergency treatments to unblock blood vessels and
preliminary indications that vitamin D might help prevent multiple
sclerosis in women, a finding which researchers are following up.

Of the NINDS clinical research studies, approximately 125, with more
than 25,000 expected participants, are clinical trials of interventions
to prevent or treat neurological disorders. Projects range from planning
and pilot trials to large multi-center trials. In notable results this
year, a small intramural clinical trial of multiple sclerosis patients
who did not respond to interferon, the standard therapy, found that
administering the genetically engineered antibody daclizumab improved
outcome substantially. An extramural clinical trial found that
ultrasound may improve the effectiveness of t-PA (tissue plasminogen
activator) in breaking up clots and restoring blood flow to the brain.
T-PA has been the only FDA-approved therapy for acute ischemic stroke
since NINDS clinical trials demonstrated its effectiveness in the
1990's.

In other clinical trials activities this year, the innovative
Neuroprotection Exploratory Trials in Parkinson Disease (NET-PD) program
is selecting drugs that show promise for slowing the course of Parkinson
disease and testing them through a clinical trials network. From 59 drug
candidates proposed by 42 scientists from 13 countries, 4 drugs were
selected for testing in phase II clinical trials, with results expected
in the next few months. If results warrant, larger trials will follow
quickly. To enhance drug selection in the future, the NINDS is
establishing a contract animal testing facility. The NINDS Pilot Studies
Network (NPTUNE) is also underway to expedite pilot trials of new
treatments for rare neurological disorders, for which the lack of
clinical trials infrastructure often blocks moving therapies forward.
NPTUNE chose testing of phenylbutyrate for spinal muscular atrophy (SMA)
as the first trial. Development of the Clinical Research Collaboration
(CRC) has also begun, which will extend the reach of the NIH into more
communities across the U.S. The CRC will engage hundreds of community
practice and academic neurologists to speed trials; minimize costs; make
trials more accessible to patients; recruit a diverse spectrum of
participants; facilitate trials of rare diseases; and improve transfer
of research results to clinical practice in community settings.
Complementing the CRC, the NINDS is building a network to develop
emergency treatments for neurological disorders. Stroke, seizures, and
traumatic injury are just a few of the neurological disorders that often
require emergency treatment. This program brings together specialists in
emergency medicine with experts in neurological disease and in clinical
trials. Finally, the NINDS is fully engaged in Roadmap initiatives to
address clinical research and trials issues that cut across all of
medical science.

TRANSLATIONAL RESEARCH

Translational research encompasses the many steps that move basic
research findings to a therapy that is ready for testing in clinical
trials. In 2002, the NINDS began a comprehensive translational research
program that can apply to all diseases within its mission. The program
solicits investigator-initiated proposals, evaluates them according to
peer review criteria tailored to the needs of translational research,
and monitors progress with milestone-driven funding, as is common in
industry. The first major project in this program, the Parkinson's Gene
Therapy Study Group, met critical milestones this year with the creation
of a stable colony of parkinsonian non-human primates for testing
therapies and the development of modified viral vectors that can deliver
therapeutic genes under tight control.

Complementing the broad translational research program and relevant
Roadmap initiatives in areas such as molecular libraries are several
specific NINDS efforts. In one such program, the Institute, working with
academia and voluntary disease organizations, formed a consortium of 26
laboratories to screen a set of 1040 known drugs with laboratory tests
for potential use against neurodegenerative diseases. Most of the drugs
in this set have been approved by the U.S. Food and Drug Administration
(FDA) for other uses, and so might move more quickly toward clinical
trials. Several drugs from this program have shown promise against
neurodegeneration and moved forward to testing in more definitive mouse
models of human diseases. One drug, ceftriaxone, has already proceeded
to testing in a clinical trial for ALS early this fall.

Because of the state of the science and the impact of SMA on children
and families, the NINDS chose this disease as the focus of an innovative
approach to expedite therapy development. The SMA Project uses a
performance-based contract mechanism to accelerate all steps from
recognition of a research need, through solicitation, review, and
funding of targeted research subprojects. In its first year, the Project
quickly developed detailed plans for SMA drug development and solicited
targeted research subprojects. A September 2004 workshop engaged SMA
researchers, clinicians, and voluntary health organizations on clinical
trials. As the Project proceeds, the NINDS is evaluating whether the
approach might be applied to other disorders.

The NINDS continues to support teams of researchers focused on
developing therapies for neurological diseases through several other
programs. These programs emphasize basic, translational, or clinical
research, as appropriate to the state of science for each disorder.
Examples include the Senator Paul D. Wellstone Muscular Dystrophy
Cooperative Research Centers, the Morris K. Udall Centers of Parkinson's
Disease Research, the Facilities of Research Excellence in Spinal Cord
Injury, and the Specialized Programs of Translational Research in Acute
Stroke.

BASIC RESEARCH

Preventing and treating neurological disorders relies on understanding
the normal workings of the nervous system and what goes wrong in
disease. The emerging new modalities for combating disease highlight
this: Stem cells and growth factors arose from fundamental studies of
nervous system development. Deep brain stimulation, which shows promise
for Parkinson, dystonia, Tourette syndrome, and other diseases, relies
upon research techniques developed to monitor the activity of single
nerve cells in the brain, and on basic knowledge of anatomical circuits
that control movement. Studies of how the brain learns are leading to
behavioral therapies that may enhance "brain plasticity" to repair
damage and giving new insights into what causes chronic pain, epilepsy,
and dystonias. Most current drugs for nervous system diseases target
molecules identified for their role in normal brain function. Gene
therapy, new understanding of the molecular basis of diseases,
diagnostic tests, and animal models for testing therapies are among the
many fruits of fundamental studies in neurogenetics.

Basic neuroscience research is continuing to advance rapidly, and
Roadmap initiatives in areas such as protein structure, computational
biology, and nanomedicine will help to accelerate that pace. Among the
many basic neuroscience findings this year are studies that give
insights into what controls stem cells in the brain and how they might
be used therapeutically, the role of estrogen in autoimmune disease,
strategies to transfer therapeutic genes into muscles to treat
dystrophies, insights into the molecular targets of nicotine, better
understanding of how genes and experience interact in brain development,
and a new approach to silencing harmful genes in diseases such as
Huntington's and spinocerebellar ataxias.

THE NIH BLUEPRINT FOR NEUROSCIENCE RESEARCH

Over the last several years, the NIH Institutes and Centers that have an
interest in the nervous system have increasingly joined forces, driven
by advances in neuroscience that have revealed common issues that
intersect their unique missions. The NIH Blueprint for Neuroscience is a
framework to enhance that cooperation. Just as the NIH Roadmap addresses
the roadblocks that hamper progress across all of medical science, the
NIH Blueprint for Neuroscience takes on challenges in neuroscience that
are best met collectively. By pooling resources and expertise, the 15
NIH Institutes and Centers that make up the Blueprint can take advantage
of economies of scale, confront challenges too large for any single
Institute, and develop research tools and infrastructure that will serve
the entire neuroscience community. The Blueprint is developing an
initial set of initiatives focused on tools, resources, and training
that can have a quick and substantial impact because each builds on
existing programs. These initiatives include an inventory of
neuroscience tools funded by the NIH and other government agencies,
enhancement of training in the neurobiology of disease for basic
neuroscientists, and expansion of ongoing pediatric imaging, gene
microarray, and gene expression database efforts. For FY06, Blueprint
initiatives focus on genetically

engineered mouse strains to study the nervous system, neuroscience
training programs, and specialized "core" resources that can be shared
across many laboratories.

Thank you, Mr. Chairman. I would be pleased answer questions from the
Committee.

Number range CHAPTERDepartment 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 has increased research cooperation and collaboration, and has
resulted in the construction of the new NIH Neuroscience Research
Center, Phase I of which has opened on the NIH campus.

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.

Number range CHAPTERDepartment of Health and Human Services

Office of Budget

William R. Beldon

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in
the Department of Health and Human Services. He has been a Division
Director in the Budget Office for sixteen years, most recently as
Director of the Division of Discretionary Programs. Mr. Beldon started
in federal service as an auditor in the Health, Education and Welfare
Financial Management Intern program. Over the course of more than 30
years in the Budget Office, Mr. Beldon has held Program Analyst, Branch
Chief and Division Director positions. Mr. Beldon received a Bachelor's
Degree in History and Political Science from Marshall University and
attended the University of Pittsburgh where he studied Public
Administration. He resides in Fort Washington, Maryland.