NINDS to Support Eight New
Parkinson’s Disease Research Centers of Excellence
As part of its efforts to defeat Parkinson’s
disease, the National Institute of Neurological
Disorders and Stroke (NINDS) today announced plans to
award new grants to eight top universities. The new
awards will raise to eleven the number of Parkinson’s
Disease Research Centers of Excellence the Institute
funds and represent a total commitment of $49 million to
be spent over the next 5 years. Added to the $24
million committed to three such centers in September of
1998, this brings total Institute funding for the
Parkinson’s Disease Research Centers of Excellence
program to $73 million.
“Opportunities for conquering Parkinson’s
disease have never been greater,” says Gerald D.
Fischbach, M.D., director of the NINDS. “We are
confident that knowledge of the fundamental processes
underlying this debilitating disease will, in turn, lead
to improved diagnosis and treatment. The Centers’
multidisciplinary framework provides the collaborative
environment necessary to take full advantage of emerging
discoveries in the basic and technological sciences that
are the prelude to clinical advances. It is my hope
that the scientists at the different Centers will work
together whenever possible.”
The Parkinson’s Disease Research Centers of
Excellence program was developed in response to Senate
bill 535, also known as the Udall bill in honor of
former Congressman Morris K. Udall, who died in December
1998 after a long battle with Parkinson’s disease. In
making today’s announcement,
Dr. Fischbach noted that the Centers will henceforth be
called the Morris K. Udall Parkinson’s Disease Research
Centers of Excellence.
The eight new Udall Centers are located at
Brigham and Women’s Hospital Center for Neurologic
Diseases in Boston, Massachusetts; the Neurological
Institute at Columbia University in New York City; the
University of Virginia Health System in Charlottesville;
the Mayo Clinic in Jacksonville, Florida; the University
of Kentucky in Lexington; Duke University in Durham,
North Carolina; the University of California at Los
Angeles (UCLA); and Harvard Medical School and McLean
Hospital in Belmont, Massachusetts. They will join the
NINDS Parkinson’s Disease Research Center programs
already under
(more)
way at Emory University in Atlanta, Georgia;
Massachusetts General Hospital in Boston; and The Johns
Hopkins University School of Medicine in Baltimore,
Maryland. Most of the Centers will also provide state-
of-the-art, multidisciplinary training for young
scientists preparing for research careers investigating
Parkinson’s disease and related neurodegenerative
disorders.
Peter T. Lansbury, Jr., Ph.D., will lead the
Parkinson’s disease research team at the Brigham and
Women’s Hospital Center for Neurologic Diseases in
Boston. The Massachusetts group seeks to elucidate the
origins of Parkinson’s disease by studying the structure
and function of three proteins—alpha synuclein,
ubiquitin C-hydrolase, and parkin—all of which are
implicated in the development of two kinds of familial
Parkinson’s disease. Knowledge of how these proteins,
which are the products of the mutant genes in these
families, cause the clinical symptoms of Parkinson’s
disease should lead to the development of new drugs that
target that process. The investigators also plan to
develop new and better animal models to further study
the pathogenesis of Parkinson’s disease and screen
potential therapeutic compounds.
Stanley Fahn, M.D., an international authority
on Parkinson’s disease, will oversee the Udall Center in
New York City at the Neurological Institute at Columbia
University. His group will use animal models and cell
cultures to study various mechanisms of cell death,
including the possible roles of hypochlorous acid,
oxidative stress, and three proteins that may be
involved in apoptosis, a kind of cellular suicide.
Other members of the Columbia team hope to identify new
genes that, when either expressed or suppressed,
contribute to the degeneration of key nerve cells. In
addition to conducting these basic studies, Center
scientists will attempt to develop better methods for
assessing the progression of Parkinson’s disease using
an imaging technique known as positron emission
tomography, or PET. If they are successful, future
clinical trials of therapeutic agents for Parkinson’s
disease could involve fewer patients and be completed
more quickly than is currently the case. Finally, the
New York group will investigate gender and ethnic
differences in people with Parkinson’s disease.
Specifically, they will examine the role of risk factors
in men versus women and blacks versus whites, studies
which could lead to improved care for certain groups of
patients.
In Charlottesville, scientists at the University
of Virginia Health System will build upon their
pioneering investigations of the role of mitochondrial
mutations in Parkinson’s disease. Mitochondria are
microscopic, energy producers that function as “power
plants” within cells. It has been suggested that
specific mutations in mitochondrial DNA may be the cause
of Parkinson’s disease when it is not inherited. Under
the direction of G. Frederick Wooten, M.D., the
Charlottesville Center’s research team will attempt to
confirm this association, determine which mitochondrial
defects are implicated, and define the mechanisms by
which defective mitochondria may trigger cell death,
oxidative stress, and other changes in Parkinson’s
disease.
John A. Hardy, Ph.D., is internationally known
for his research on neurodegenerative disorders. His
team at the Mayo Clinic’s Jacksonville facility will
attempt to clone two genes, one on chromosome 4 and one
on chromosome 2, that are believed to be involved in
familial forms of Parkinson’s disease. Once the
(more)
genes are cloned, their functions could be studied and
the results evaluated for relevance to the more common,
sporadic type of Parkinson’s disease. The group will
also endeavor to create a new and better mouse model
that will clarify the role of alpha-synuclein and other
proteins in cell death and degeneration. If successful,
such a model could prove invaluable in studies of new
treatments for Parkinson’s disease.
It has been suggested that nerve growth factors,
particularly GDNF, may be therapeutic in Parkinson’s
disease. Led by Greg A. Gerhardt, Ph.D., Udall Center
scientists at the University of Kentucky will study the
behavioral, functional, and anatomical effects of GDNF
in a laboratory model of Parkinson’s. Using an infusion
pump, the investigators will deliver GDNF to two brain
sites over a period of time to determine whether GDNF
can protect or restore the function of damaged nerve
cells without unwanted side effects. The group will
also examine the effects of stopping and starting GDNF
therapy. Such studies could lay the groundwork for
human trials of GDNF and similar neuroprotective agents.
Jeffery M. Vance, M.D., will direct the Udall
Center at Duke University. The Duke team will use
several state-of-the-art methods to find genes that may
contribute to the etiology of both the familial and
sporadic types of Parkinson’s disease. During autopsy
of people with one of the two forms of the disease and
of people without the disease, they will hunt for genes
that are over-expressed or under-expressed in the
substantia nigra, a part of the brain severely affected
in Parkinson’s disease. Such genes are likely to play a
role in the cause of the disease. After the candidate
genes are identified, the scientists will search for
evidence of the genes in patients with either familial
or sporadic Parkinson’s disease and their siblings.
Such research may allow investigators to distinguish the
genes that contribute to familial Parkinson’s from those
involved in sporadic cases.
At UCLA, Marie-Francoise S. Chesselet, M.D.,
will lead studies designed to elucidate the role played
by a part of the brain called the subthalamic nucleus in
treated and untreated Parkinson’s disease. It is
believed that the loss of the brain chemical dopamine, a
hallmark of Parkinson’s disease, causes molecular and
cellular changes in the subthalamic nucleus. Dr.
Chesselet’s group will compare the changes produced in
the brains of rats with a Parkinson’s-like disease when
the animals are given one of three treatments:
levodopa, the standard therapy for Parkinson’s disease;
deep brain stimulation; or implants of genetically
engineered cells. They will then evaluate postmortem
brain tissue from patients with Parkinson’s to see
whether the parkinsonian changes seen in the rat models
also occurred in the patients. By clarifying the
functional connections among the parts of the brain most
affected in Parkinson’s disease, such studies could pave
the way for the development of new treatments for people
with the disease.
Ole Isacson, M.D., will direct the Udall Center
at Harvard University Medical School and McLean Hospital
in Belmont, Massachusetts. His team will study several
novel treatments for Parkinson’s disease in animal
models. One project will evaluate the ability of a new
compound with neuroprotective properties to prevent and
reverse parkinsonism in primates. Another project will
expand on tissue implantation research. Previous
implantation investigations have been limited to single
transplants into the part of the
brain called the striatum. Dr. Isacson’s group will use
a primate model to examine the effect of multiple
(more)
fetal or stem cell implants into the striatum and the
substantia nigra and subthalamic nucleus, other areas of
the brain that are affected by the dopamine loss
characteristic of Parkinson’s disease. They will also
transplant embryonic mouse tissue into rodent and
primate Parkinson’s models. Behavioral measurements,
imaging studies using PET and magnetic resonance
spectroscopy, and post-mortem tissue studies will be
used to evaluate the efficacy of the therapies.
Benefits seen in any of these animal studies could lead
to clinical trials in humans with Parkinson’s disease.
“The NINDS is dedicated to supporting a broad
and varied program of Parkinson’s disease research,”
says Dr. Fischbach. “Clinical breakthroughs are likely
to come, not from one, but from a multitude of fields.
It is our goal to provide the support necessary not only
to conduct widely diversified Parkinson’s disease
research programs, but to foster collaboration and the
open exchange of ideas among program investigators.”
More than half a million Americans have
Parkinson's disease, a neurological disorder of later
life, that progressively impairs control of body
movement, interferes with walking and talking, and often
leads, over time, to rigid immobility. Symptoms of
Parkinson's disease include tremor (particularly tremor
of a body part at rest), stiff limbs, slow or absent
movement, lack of facial expression, a shuffling gait,
and a distinctive stoop. Other symptoms, such as
depression and impaired ability to think, may also
develop, especially during the later stages of the
disease. These symptoms result from degeneration of
nerve cells in the brain, particularly those involved in
the production of the chemical dopamine. Although
standard treatment with the drug combination
levodopa/carbidopa can restore virtually normal movement
to many people with Parkinson’s early in the disease's
course, the treatment loses effectiveness as the disease
progresses.
The NINDS, part of the National Institutes of
Health located in Bethesda, Maryland, is the nation's
leading supporter of research on the brain and nervous
system and a lead agency in the Congressionally
designated Decade of the Brain. The NINDS celebrates its
50th anniversary in the year 2000.
