[Senate Hearing 107-655]
[From the U.S. Government Publishing Office]
S. Hrg. 107-655
PARKINSON'S DISEASE RESEARCH
=======================================================================
HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED SEVENTH CONGRESS
SECOND SESSION
__________
SPECIAL HEARING
MAY 22, 2002--WASHINGTON, DC
__________
Printed for the use of the Committee on Appropriations
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COMMITTEE ON APPROPRIATIONS
ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii TED STEVENS, Alaska
ERNEST F. HOLLINGS, South Carolina THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont ARLEN SPECTER, Pennsylvania
TOM HARKIN, Iowa PETE V. DOMENICI, New Mexico
BARBARA A. MIKULSKI, Maryland CHRISTOPHER S. BOND, Missouri
HARRY REID, Nevada MITCH McCONNELL, Kentucky
HERB KOHL, Wisconsin CONRAD BURNS, Montana
PATTY MURRAY, Washington RICHARD C. SHELBY, Alabama
BYRON L. DORGAN, North Dakota JUDD GREGG, New Hampshire
DIANNE FEINSTEIN, California ROBERT F. BENNETT, Utah
RICHARD J. DURBIN, Illinois BEN NIGHTHORSE CAMPBELL, Colorado
TIM JOHNSON, South Dakota LARRY CRAIG, Idaho
MARY L. LANDRIEU, Louisiana KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island MIKE DeWINE, Ohio
Terrence E. Sauvain, Staff Director
Charles Kieffer, Deputy Staff Director
Steven J. Cortese, Minority Staff Director
Lisa Sutherland, Minority Deputy Staff Director
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Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
TOM HARKIN, Iowa, Chairman
ERNEST F. HOLLINGS, South Carolina ARLEN SPECTER, Pennsylvania
DANIEL K. INOUYE, Hawaii THAD COCHRAN, Mississippi
HARRY REID, Nevada JUDD GREGG, New Hampshire
HERB KOHL, Wisconsin LARRY CRAIG, Idaho
PATTY MURRAY, Washington KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana TED STEVENS, Alaska
ROBERT C. BYRD, West Virginia MIKE DeWINE, Ohio
Professional Staff
Ellen Murray
Jim Sourwine
Mark Laisch
Adrienne Hallett
Erik Fatemi
Bettilou Taylor (Minority)
Mary Dietrich (Minority)
Sudip Shrikant Parikh (Minority)
Candice Rogers (Minority)
Administrative Support
Carole Geagley
C O N T E N T S
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Page
Opening statement of Senator Tom Harkin.......................... 1
Opening statement of Senator Arlen Specter....................... 3
Statement of Hon. Debbie Stabenow, U.S. Senator from Michigan.... 4
Opening statement of Senator Patty Murray........................ 5
Statement of Hon. Paul Wellstone, U.S. Senator from Minnesota.... 5
Statement of Audrey S. Penn, M.D., Acting Director, National
Institute of Neurological Disorders and Stroke, National
Institutes of Health, Department of Health and Human Services.. 6
Prepared statement........................................... 8
Statement of Dr. Ole Isacson, director, Center on
Neuroregeneration Research, McLean Hospital and Harvard Medical
School......................................................... 13
Prepared statement........................................... 14
Statement of Joan Samuelson, founder and president, Parkinson's
Action Network................................................. 17
Prepared statement........................................... 19
Statement of Don Schneider, Parkinson's patient, Clinton, IA..... 21
Prepared statement........................................... 23
Statement of Muhammad Ali, former heavyweight boxing champion,
accompanied by Lonnie Ali...................................... 25
Prepared statement........................................... 27
Statement of Michael J. Fox, founder, the Michael J. Fox
Foundation for Parkinson's Research............................ 28
Prepared statement........................................... 31
Prepared statement of Senator Thad Cochran....................... 42
Letter from Do No Harm: The Coalition of Americans for Research
Ethics......................................................... 42
PARKINSON'S DISEASE RESEARCH
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WEDNESDAY, MAY 22, 2002
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 9:42 a.m., in room SH-216, Hart
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
Present: Senators Harkin, Murray, and Specter.
opening statement of senator tom harkin
Senator Harkin. Good morning, everyone. The Senate Labor,
Health and Human Services, and Education Appropriations
Subcommittee will now please come to order.
Three weeks ago, this subcommittee held a hearing on
Alzheimer's disease, a condition that destroys the mind while
leaving the body basically intact. Today we will discuss its
biological opposite, Parkinson's disease, a condition that
destroys the body while the mind stays fully aware of what is
happening.
This is a devastating disease, as we will hear from our
witnesses. But a cure is finally in sight. Scientists have made
exciting advances against Parkinson's in the past year alone,
particularly in the areas of embryonic stem cell
transplantation, deep brain stimulation, and possible
environmental and chemical causes of the disease. Many
researchers believe that Parkinson's will be cured sooner than
any other major neurological condition, possibly within the
decade.
This progress would not have been possible without the
National Institutes of Health, which supports 11 Udall Research
Centers across the country, among many other efforts to cure
Parkinson's. Senator Specter and I have led the effort to
double funding for the NIH over 5 years, and I am proud to say
we will complete that goal this year.
I am concerned, however, by the fact that NIH funding for
Parkinson's has not kept pace with our doubling effort. This
has occurred despite increasingly strong language in the Labor-
HHS appropriations bills. So, I will pay close attention to
NIH's plans for Parkinson's research in the years to come.
We have an outstanding panel of witnesses this morning. I
would like to give a couple special welcomes, first to Don
Schneider, who traveled here from my home State of Iowa to tell
us about his experience with Parkinson's. Don, I thank you and
your wife, Rita, for being with us.
Of course, I would like to welcome the greatest, to me the
greatest athlete, perhaps one of the greatest human figures of
the 20th century, Muhammad Ali.
Muhammad, your efforts to promote peace around the world
and to help people in need are as legendary as your victories
in the boxing ring. I know that I was, as much as anyone in
this room and all over the world, so thrilled when you lit the
torch at the Olympics. It brought back so many memories.
I think one of the great legacies, Muhammad, of your life
and your career is you teach people never to give up. If you
get knocked down, get up and come back again. I think that is
the hope and I think that is the courage that you give everyone
in this room and everyone who is afflicted with Parkinson's. We
may have had setbacks, but we are getting up and we are coming
back again. So, we thank you for giving us that courage and
that leadership. We are honored to have you here today.
I also offer my warm welcome to Michael J. Fox. You may
know him from Spin City and Family Ties or many successful
films. But now that he has hit the New York Times Best Seller
List with his memoir, titled Lucky Man, he may have found his
true calling in being an author. Again, Michael Fox, thank you
very much.
We are also honored and fortunate to have with us today
three former Senators. Let's hear it for Claiborne Pell, our
former Senator from the State of Rhode Island.
Next to him another great Senator, Charles Mac Mathias, of
Maryland.
And he could not be here, but his better half and someone
who we enjoyed being with for so many years and still do,
Carolyn Long, wife of former Senator Russell Long.
Brock Adams was supposed to be here. I understand he is on
his way, and I will introduce him when he arrives.
All four of these Senators have Parkinson's. We miss them
greatly here in the Senate, but we are honored that you could
be here today.
Finally, I would recognize one other special person, Ruth
Kirschstein. Get ready, Ruth, because we have a surprise for
you. Dr. Kirschstein began her career at NIH in 1956. She has
held numerous positions there including Director of the
National Institute of General Medical Sciences, Acting Director
of the NIH, and her current position, Deputy NIH Director.
Ruth is a visionary and has been a tremendous leader during
her service at NIH, playing a key role in launching the Human
Genome Project and promoting women's health research.
Throughout her career at NIH, there is one thing she has always
paid particular attention to and that is the next generation of
scientists, building up programs that encourage our best and
brightest to enter the field of medical research.
So, it gives me great pleasure to announce this morning
that Senator Specter and I, along with Chairman Regula and
Congressman Obey in the House, have inserted language in the
upcoming supplemental appropriations bill that will rename the
National Research Service Awards program the Ruth L.
Kirschstein National Research Service Awards.
Congratulations, Ruth, and thank you for your decades of
service to our Nation. We look forward to many years of
continued service at the NIH.
Now I would yield to my great friend, Senator Specter, for
his opening remarks.
opening statement of senator arlen specter
Senator Specter. Thank you very much, Mr. Chairman, and
good morning, ladies and gentlemen.
This overflow audience is a testament to the importance of
curing Parkinson's. It is a matter which this subcommittee has
been working on very hard for many, many years. As Senator
Harkin outlined, we set out to double the funding for the
National Institutes of Health. It has been moved from $13
billion to $23 billion, and the President has recommended in
this year's budget an additional $3.7 billion; which will more
than reach the doubling goal--possibly exceed our goal to
double funding.
People ask what is next, and I say: ``Well, the next step
is to triple the funding for NIH.''
We are a very wealthy country with a gross national product
in the range of $10 trillion and a Federal budget in excess of
$2 trillion. Also, it is a matter of establishing priorities,
and there is nothing more important than health. The increase
in funding has given the scientists the opportunity to do
intensive research and clinical studies. The experts who
appeared here recently from the National Institutes of Health
on neurological diseases thought that we may have the cure for
Parkinson's within 5 years. It is not a guarantee, but it is an
estimate.
We face a very difficult challenge, ladies and gentlemen.
Now pending before the Senate, and up for a vote in the course
of the next several weeks, is a procedure called nuclear
transplantation. It is commonly referred to as therapeutic
cloning, and that is a misnomer. It is not cloning at all.
There is an agreement against cloning to create another person,
but when you have the procedure nuclear transplantation, it is
accomplished by taking the DNA, for example, from a person who
has Parkinson's so that the stem cell is consistent with that
person and will not be rejected.
Regrettably the House of Representatives has criminalized
this procedure which is, to my way of thinking, an absolute
anathema, and we have to stop that in the U.S. Senate. When we
have had crowds, audiences overflowing in this room on
Alzheimer's and breast cancer and heart disease and many other
ailments, Senator Harkin and I have sounded the bugle to have
Americans tell their Senators not to criminalize an important
medical procedure that may conquer so many, many diseases.
That is what we are calling on today.
There is a great deal more that could be said, but we have
a very distinguished group of witnesses here today. As Senator
Harkin has noted, we are especially grateful to Muhammad Ali
and Michael J. Fox, who, when they come here, attract a lot of
attention because there is so much admiration for what they
have done. And that kind of attention stimulates public
response to our call to influence Senators to allow us to
continue the indispensable research to cure Parkinson's and
many other maladies.
When The Champ took his bow, he looked pretty strong to me.
He looked pretty resilient. I think he might still go 10 rounds
under the proper circumstances. See, there he goes.
When we met in the back room, he walked in with Michael J.
Fox, and I told him not to be too tough on Michael just because
Michael was bigger and stronger than The Champ was.
And we thank Michael J. Fox for all that he has done. He
has been in this room on many occasions and his efforts have
been very instrumental in leading this subcommittee to move
ahead with the funding for the National Institutes of Health.
So, we have come a long way, but we have got a long way to
go, and our work is cut out for us. Anybody within sound of our
voices, contact your Senators. Thank you.
Senator Harkin. Thank you very much, Senator Specter.
Although not a member of the committee, she wanted to be
here to recognize her perhaps most famous constituent, Senator
Stabenow of Michigan.
STATEMENT OF HON. DEBBIE STABENOW, U.S. SENATOR FROM
MICHIGAN
Senator Stabenow. Well, thank you, Mr. Chairman. I also am
here as a family member of a grandmother who had Parkinson's
disease and want to thank you very much for your leadership,
Senator Harkin and Senator Specter. I am committed to do
whatever we need to do to get the job done.
I am very much appreciative of the opportunity, before
leaving to go preside over the session, to help introduce our
most famous Michiganian in the world, from Berrien Springs,
Michigan, Muhammad Ali and Mrs. Ali. Welcome. It is a great
pleasure. We are very, very proud that you are Michigan
residents. There is no question that from his career in the
ring to his global diplomatic efforts to his many charities and
philanthropic work, Muhammad Ali has been a role model to all
of us. We in Michigan are particularly proud of that.
I did want to comment, though, that particularly in the
days after September 11, when fear really threatened to divide
all of us, I was very proud that it was Muhammad Ali who
stepped forward and issued a call for unity and tolerance. So,
in addition to all that you are doing, in addition to the fact
that you are here today, I have quoted you frequently in
saying: ``Rivers, ponds, lakes, and streams, they all have
different names, but they all contain water. So religions have
different names, but they all contain the truth.'' So, I want
to thank you for those words at a time that was very critical
for our country.
You have fought a lot of battles in a lot of rings, and I
know that you are here today to focus on your greatest battle,
the fight against Parkinson's disease, one that you share with
millions of Americans. We want you to know that for those of us
here today, we are in the fight with you and we thank you very
much for your heart and your strength and your courage. Thank
you.
Senator Harkin. Thank you very much, Debbie.
I would recognize Senator Murray for an opening statement
and then Senator Wellstone.
opening statement of senator patty murray
Senator Murray. Thank you very much, Mr. Chairman, and
thank you to your leadership, to Senator Specter, and to all of
the people here who are fighting for such an important cause.
As I have shared with you before, my father had multiple
sclerosis and from the time I was 15 until he died a few years
ago, my mother was his caregiver. We hold the hope that so many
thousands of Americans do for research so that other families,
other people do not have to live through the really tough,
tough times that I have known and my family has known. But his
spirit carries with me.
I share all your hopes and dreams that stem cell research
will provide the answers for so many people. We simply cannot
allow political decisions to jeopardize what is out there, the
promise of hope for so many families.
So, thank you very much, and thank you to all of our
witnesses today.
Senator Harkin. Thank you, Senator Murray.
Perhaps one of our strongest voices and supporters in this
fight against Parkinson's, my neighbor to the north, Senator
Paul Wellstone.
STATEMENT OF HON. PAUL WELLSTONE, U.S. SENATOR FROM
MINNESOTA
Senator Wellstone. Thank you. Thank you, Mr. Chairman. I am
not a member of the committee, and it is gracious of you to let
me make an opening statement. I will stay under an hour for my
opening statement.
Senator Specter has been equally gracious.
I think the only thing to say is I want to thank you, Mr.
Chairman, for your commitment. I want to thank the panelists,
and of course, Mr. and Mrs. Ali and Michael J. Fox, and Joan
Samuelson, whom I have known for so many years. But I would
like to thank everyone else. I see Senator Pell here and I just
want to thank all of you who are here today. Thank you for your
courage. Milly, thank you for being here. There are so many
heroes and heroines.
I think the one thing I want to say is that this hearing I
approach with a sense of history because I do not think time is
neutral, and I think it is terribly important. I had a chance
to help write the Mo Udall bill, and we now have the Center of
Excellence and the focus, but we need the resources. Time is
not neutral. And everybody is here today to make sure that we
have that research focus and that we find the cure. It is so
important.
And none of this would happen except for the fact--look at
this room, Mr. Chairman. Look at all of the men and women who
have had the courage to tell their own stories. Joan, look how
far this has come. But the whole point is to now have the
resources and to have the focus and to find the cure.
I would like to thank everybody. It is an honor to be here.
Senator Harkin. Thank you very much.
There is just one other person I'd like to recognize before
I go to Dr. Penn to lead off our witnesses--someone who is
really in the forefront of this fight, giving voice to it by
writing a wonderful book about his wife--Mort Kondracke. Mort
Kondracke has been a great hero.
We also are blessed to have with us the former staff member
of Senator Claiborne Pell, who is now the Senator from Rhode
Island, Jack Reed. Senator Jack Reed is here with us too.
Now we will go to our witnesses. We have all of your
statements. They will be made a part of the record in their
entirety. I would ask if you could summarize your statements in
less than 10 minutes. Then we can get into some questions.
STATEMENT OF AUDREY S. PENN, M.D., ACTING DIRECTOR,
NATIONAL INSTITUTE OF NEUROLOGICAL
DISORDERS AND STROKE, NATIONAL INSTITUTES
OF HEALTH, DEPARTMENT OF HEALTH AND HUMAN
SERVICES
Senator Harkin. Again, Dr. Penn is the Acting Director of
the National Institute of Neurological Disorders and Stroke.
She was named the Deputy Director of NINDS in 1995. Dr. Penn,
welcome to the committee.
Dr. Penn. Thank you, Mr. Chairman. I am accompanied today
by Dr. Diane Murphy, the Program Director in neurodegeneration,
who is right behind me.
I would like to share with you the NIH studies and plans
for Parkinson's disease. NIH and particularly NINDS have been
heavily invested in supporting critical research in Parkinson's
disease for over 3 decades. Indeed, over fiscal years 1996 to
2001, NIH funding for Parkinson's research rose by 126 percent
and NINDS funding by 91 percent.
We have supported the research which delineated the
usefulness of L-dopa, mapped the critical brain circuits
affected by Parkinson's disease, and developed critical animal
models. NINDS expanded these efforts by establishing the Morris
K. Udall Centers of Excellence for Parkinson's Disease
Research, and these centers include investigators who are
working on almost every area identified as a priority by the
Parkinson's Disease Research Agenda, which was developed in
2000, in collaboration with the research and advocacy
communities, and we revisited it last January.
Parkinson's, as many of you know and as was said, is a
debilitating neurodegenerative disease caused by progressive
loss of dopamine nerve cells in the brain regions that control
movement. Abnormal protein aggregates, which are called Lewy
bodies, are seen in dopamine nerve cells, and cardinal clinical
signs are tremor, rigidity, and slow movements.
Now, Parkinson's patients need therapies that can restore
function and replace the missing nerve cells. Although
levodopa, which replaces lost dopamine, restores function for a
while, 75 to 80 percent of nerve cells are already lost when
the first signs are evident. So, we need to protect, restore,
and replace nerve cells in the specific brain centers.
So, important new evidence has emerged which is converging
to shed light on how these cells are damaged. The availability
of families with multiple members affected with Parkinson's
allowed identification of genes, and then the defective
proteins now known to be important to mechanisms of normal
protein clearance and also to degeneration in Parkinson's. The
abnormal proteins in the familial forms fold into aggregates,
accumulate in and are toxic to dopamine nerve cells.
There is new evidence that rotenone, a commonly used
pesticide which produces oxidative damage, also causes these
proteins to aggregate, Lewy body-like aggregates, and damages
dopamine nerve cells and causes severe loss of movement in
rodents.
So, based on the better information on the mechanisms of
damage, we have funded the infrastructure for design and
testing of drugs that have the potential for protecting
dopamine nerve cells against the causes of Parkinson's by
slowing the degeneration, and drugs chosen on the basis of
pilot studies will ultimately move into large clinical trials.
In the meantime, we are evaluating available results and
promoting the clinical trials of deep brain stimulation, a
surgical therapy that can achieve excellent control. DBS,
however, involves implantation of electrodes into specific deep
brain centers, and they have to be specifically implanted. It
can be used on both sides of the brain, and it can restore
nearly normal motor performance.
We have helped to design a study initiated by the Veterans
Administration to compare best medical management with DBS in
over 300 patients, and our funds will support the patients from
the affiliated academic health centers to provide a larger and
more diverse study group.
Now, cell replacement is another strategy for therapy in
advanced Parkinson's, and we long have supported studies of
embryonic stem cells from rodents in these studies.
Investigators are now reporting success in driving murine
pluripotent ES cells toward a neural fate and even to dopamine
nerve cells. There have been a few successful reversals of
motor disorders in rat models of Parkinson's simply by
implanting undifferentiated mouse ES cells.
Fetal tissue transplantation demonstrated successful
replacement of dopamine nerve cells in Parkinson's patients.
There was no immune rejection, but very little impact on the
clinical signs, and that is an absolute necessity. We must do
that.
Our own intramural investigators have obtained approved ES
cell lines, and are working to direct them to become dopamine
nerve cells before investigating implantation either into the
animal models or ultimately into human brain.
We are committed, within the President's stem cell policy,
to encouraging investigators to expand these studies. Grant
solicitations in areas such as gene therapy, stem cells,
environmental and genetic risk factors, drug screening, and
surgical therapies have encouraged investigators to apply their
knowledge, and numerous new grants have been awarded.
We recognize that the Congress and the Parkinson's
community have concerns about the level of funding provided to
the implementation of the research agenda in light of the
generous NIH and institute appropriations. We have actually
invested more in Parkinson's research than any other of our
major disorders, except stroke. However, workshops and planning
for others of our disorders increase with increasing
exceptional scientific opportunities for advances. And these
disorders include epilepsy, multiple sclerosis, brain tumors,
amyotrophic lateral sclerosis, spinal cord injury, muscular
dystrophy, and autism. All of these demand attention.
Maintaining an appropriate balance among the many disorders
within our mission continues to be a challenge.
prepared statement
So, we are extremely proud of the progress our
investigators have made in the science of Parkinson's disease,
which is already having an impact on therapy and ultimately
will allow the cure. With all of the institutes across NIH, and
with the collaborations with external advisors from the
research and voluntary communities, we are confident of
success.
So, thank you, Mr. Chairman. I will be pleased to answer
any questions you have.
[The statement follows:]
Prepared Statement of Dr. Audrey S. Penn
Mr. Chairman and Members of the Committee, I am Dr. Audrey Penn,
Acting Director of the National Institute of Neurological Disorders and
Stroke (NINDS). NINDS has a long history of supporting critical
research in Parkinson's disease (PD), and we are currently leading the
National Institutes of Health (NIH) effort to implement the Parkinson's
Disease Research Agenda. We have exciting progress to report, and I am
pleased to present some of the highlights of this work to you today.
background
Parkinson's disease, as many of you are aware, is a devastating and
debilitating neurological disorder caused by the progressive loss of
nerve cells that control movement. These cells produce the
neurotransmitter dopamine, and their disappearance from the brain leads
to tremors, rigidity, and slowing of movement. Other disabling effects
can also occur, including speech problems and, in some individuals,
difficulties with thinking, sleep, and depression. Parkinson's affects
more than 500,000 Americans at any given time, and its severity varies
from person to person. For some, the disease is marked by a rapidly
debilitating physical deterioration, while in others, the disease can
be managed for years with available medical therapies. Most people are
diagnosed with the disease after the age of 50, although this disorder
is not uncommon in younger people. All of these individuals need
treatments that can control their disease and eventually a cure, and we
are committed to continuing an intensified and coordinated effort to
bring research to bear on this need.
For more than three decades, NINDS has been heavily invested in PD
research. We have supported early studies of L-dopa, fundamental
research on the brain circuitry affected by PD, the development of
critical animal models, and important advances in understanding the
genetic basis of parkinsonism. In the late 1990s, NINDS expanded these
efforts by establishing the Morris K. Udall Centers of Excellence for
Parkinson's Disease Research. Selected through a competitive review
process, these Centers have proven to be a sound investment. Over the
past several years, they have developed essential collaborations and
have contributed to a wide range of research investigations, from the
genetics of PD and cellular dysfunction of neurons in the disorder, to
studies of brain circuitry, neuropathology, and preclinical testing of
therapies.
As requested by Congress, and in light of the numerous
opportunities in Parkinson's research, NINDS took its commitment to
this field one step further, by leading the development of a multi-year
scientific research plan for PD. As part of this effort, all components
of the PD community came together to evaluate progress, re-examine
plans and priorities, and identify critical research needs and new
approaches with significant promise. NIH submitted this plan, the
Parkinson's Disease Research Agenda, to Congress in March 2000.
Although we are all optimistic that the Agenda will serve as a useful
road map to developing and integrating treatments for PD, it is not
possible to predict a precise time line for major breakthroughs or a
cure for this disorder--even in a time of great scientific progress.
We believe that one of the most important results of developing the
Agenda was that it highlighted the promise of many ongoing areas, as
well as new opportunities in PD research, and the importance of
accelerating progress in all of them simultaneously. To address these
needs, NINDS and NIH staff have developed numerous grant and contract
solicitations, consortia, and workshops that complement the
investigator-initiated awards that make up the core of our grant
programs. The number of NINDS-initiated PD research activities
undertaken since the inception of the Agenda has far exceeded that for
any other disease in the history of the Institute, and the number of
NINDS staff working on PD has been expanded beyond that for other
disorders within the Institute's mission. The scientific community has
responded enthusiastically to these actions, and several significant
research efforts have resulted, including the initiation of major
clinical trials that we believe will have a significant impact on the
treatment of Parkinson's--both in individuals who have just recently
been diagnosed, and in those in the later stages of the disease.
drug therapy
For several decades, replacement of the neurotransmitter dopamine
has been the mainstay of PD therapy. The delivery of the dopamine
precursor L-dopa, as well as other drugs that stimulate the brain's
dopamine receptors, have given many people symptomatic relief, enabling
some to continue working and enjoying recreational activities for
several years after their diagnosis. However, these treatments can come
at a price--their effectiveness can diminish over time; they can cause
uncontrolled movements and other debilitating side effects; and perhaps
most importantly, they do not stop the continuing loss of nerve cells.
The identification of a therapy that could preserve dopamine
neurons--a true neuroprotective agent--would be a watershed event in PD
research. NINDS has now taken an important step towards addressing this
urgent need, building on years of research to understand the disease at
the molecular level. In September 2001, NINDS awarded funds to develop
the design and infrastructure for a large trial of drug therapies
believed to have the potential for slowing the loss of dopamine-
producing nerve cells. In order to identify the most promising
compounds for testing, NINDS solicited recommendations from academic
and industry researchers, as well as from members of the advocacy
community. Many drugs were suggested for consideration, and extramural
experts, the trial organizers, and the scientific staff of NINDS
developed detailed, objective criteria, in order to permit an unbiased
evaluation of all suggestions. NINDS asked the committee to use this
approach so that the selection of compounds for further testing would
be based solely on their scientific promise. Following the initial
pilot studies to determine proper dosing, safety, tolerability, and any
preliminary evidence of benefit in Parkinson's patients, the most
appropriate compound, or compounds, will be selected to proceed into
definitive Phase III controlled trials. These studies are expected to
enroll approximately 3,000 subjects at 42 testing centers. The results
from the pilot phase of the project are expected within the next two
years, but preliminary results from the Phase III trial are not
anticipated until approximately 2010-11. This effort represents a
significant commitment on the part of NINDS--one that will require an
investment of approximately $40 million.
surgical therapy
Even with the promise of new and improved drug treatments for
Parkinson's, critical attention is also being focused on surgical
therapies, especially for advanced PD. The U.S. Food and Drug
Administration has recently approved deep brain stimulation (DBS)--the
passage of electrical current through electrodes that are surgically-
implanted in very specific brain regions, critical to motor control--
for the treatment of advanced Parkinson's, and interest in this option
is growing steadily. NINDS' commitment to the exploration of DBS as a
therapy for PD goes back several years, and includes solicitations
targeted to several technical aspects of DBS therapy. The Institute has
now funded a number of investigators to study many basic questions
about DBS, and we have assembled these researchers into a consortium
that will meet for the first time in June 2002. In addition, NINDS is
collaborating with the Department of Veterans Affairs (VA) on the
largest clinical trial ever of DBS to treat PD. In this study, which
will enroll approximately 300 subjects at six VA sites and affiliated
academic institutions, researchers will compare stimulation of one of
two different brain regions to best medical management of Parkinson's.
If DBS is shown to be the more effective approach, subjects on medical
management will also receive DBS--and the effects of the two different
stimulation strategies will be compared. The results of the trial will
address questions of critical importance to those affected by PD now,
and NINDS support of the academic sites in this trial will enable the
appropriate enrollment of both women and minorities in the study.
cell and tissue transplantation
For people with advanced PD, who have already lost many of their
dopamine-producing nerve cells, replacement cell or tissue therapy is
another promising strategy. Studies of fetal tissue transplantation
have already demonstrated that this approach is feasible in the
treatment of PD, and advances in stem cell biology have made this
therapy a future possibility as well. NINDS has long supported research
on animal embryonic stem cells and adult stem cells, and some of this
work has demonstrated success in reversing motor impairments in animal
models of PD. We are committed, within the criteria of the President's
stem cell policy, to expanding these studies further, and to
aggressively exploring the potential of human embryonic stem cells in
treating this disorder.
research agenda implementation and scientific advances
These examples illustrate the types of targeted program activities
that have already contributed to the implementation of the PD Research
Agenda. Grant solicitations and workshops in areas such as gene
therapy, stem cells, the cellular basis of PD, environmental and
genetic risk factors, drug screening, and surgical therapies have
encouraged investigators to apply their knowledge to the field of PD
research, and numerous new grants have been awarded. Although NINDS has
initiated a number of these activities, many other NIH Institutes and
Centers (ICs) have also developed programs that are directly responsive
to the needs identified in the Agenda. For example, the National
Institute of Environmental Health Sciences (NIEHS) is currently
developing a Consortium Centers Program, that will operate as a highly
interactive national network engaged in research to understand the
potential environmental influences in the causation of PD. In addition,
multiple ICs participated in a joint exploratory grant program with
several private PD research funding organizations.
While the initiation of these actions has been a critical part of
our implementation effort, we recognize that it is ultimately the
scientific output of the Agenda that will make a difference in the
lives of people with Parkinson's. To that end, we have progress to
report on a number of fronts:
--NINDS-supported stem cell researchers and their collaborators have
found that mouse embryonic stem cells can develop into dopamine
neurons in a rodent model of Parkinson's and help reverse
impairments in motor function. Importantly, these cells exhibit
their plasticity without any manipulation beyond implantation
into the motor control regions of the brain. This work builds
upon studies of the factors that can induce cells to become
dopaminergic neurons, conducted over many years by NINDS
intramural investigators and others, and it emphasizes the need
to pursue stem cell applications within the federal policy.
--Although several genes that are involved in inherited forms of
Parkinson's disease have been identified, the influence of
particular genes on the more common forms of the disease is not
fully understood. However, researchers have now conducted
large-scale screening of the human genome and have identified
several chromosomal regions that may be involved in PD. In
particular, one study has identified small differences in the
tau gene--which codes for a protein known to play a role in
Alzheimer's disease and other neurodegenerative disorders--as a
possible susceptibility factor for Parkinson's.
--While the influence of inherited genes on the development of PD has
not been completely characterized, gene therapy is emerging as
a promising technique for restoring function in animal models
of this disorder. This work took a dramatic step forward two
years ago, when NINDS-funded investigators found that the
delivery of specific growth factors to primates with a
parkinsonian condition, using a genetically-modified virus,
could have dramatic reparative effects. Now a separate group of
researchers has added to this armamentarium, demonstrating that
a different virus--engineered to deliver enzymes critical for
the production of L-dopa--can have similarly impressive effects
in a rat model of the disorder. As researchers accumulate more
information about the safety and efficacy of different delivery
systems and treatment compounds, translational research on gene
therapy for PD can move forward.
--NINDS and the National Institute on Aging have supported research
that demonstrates exposure of rodents to the pesticide rotenone
can cause the development of anatomic and behavioral changes
that mimic those seen in PD. In addition, work supported by
NIEHS has shown that other agricultural compounds can also
produce abnormalities in cells that are similar to those
produced by PD. This mounting evidence strongly implicates
environmental toxicants in the development of PD, and along
with the genetic contributions to the disease, establishes a
framework for more extensive studies of risk factors and their
cellular effects.
--Last month, intramural researchers at NINDS published a study
showing widespread effects of PD on the sympathetic nervous
system. This system controls functions such as blood pressure
and heart rate--those we think of as automatic. Until this work
was completed, researchers did not appreciate the extent to
which the disease damages these nerves. Individuals with PD
often experience symptoms such as orthostatic hypotension, or a
drop in blood pressure upon standing, and the loss of
sympathetic nerves observed in this study may help to explain
why this occurs.
Despite the progress made by NIH-supported investigators, the task
of implementing the Agenda will require our continued attention. A
great deal of basic science research is still needed, and much of what
is known must be moved along, so it can advance into the clinic. Our
Institute is acutely aware of this need, and we are taking steps to
facilitate translational studies across all areas of disease. We expect
these plans will have a very positive impact on PD research, since many
researchers in this community are poised to move their work into
preclinical studies, and thus could take immediate advantage of such a
program.
future plans
The most valuable outcome of the Agenda has been its use as a
scientific planning tool. For the past two years, we have used the
Agenda, along with the feedback we have received from the external
scientific community through workshops and conferences, to guide our
efforts. Since the start of the PD Research Agenda, NINDS has organized
four meetings on different aspects of Parkinson's, and other NIH ICs
have supported at least six others. The January 2002 Consortium meeting
held at the request of Congress offered an additional opportunity for
the research, advocacy, and NIH communities to engage in specific
discussions about evolving needs in PD research. Among a wide range of
suggestions offered by the clinical and basic science discussants, six
emerged as priority areas from both groups:
--Participants encouraged NIH to strengthen translational, or bench-
to-bedside, research. Translational projects are often quite
different from research grants that test straightforward
hypotheses about disease causation and treatment, and are at
varying points of development along the basic to clinical
research spectrum. For several months, NINDS has been
developing a new grant program that will attract proposals that
bridge basic studies with model development and preclinical
evaluation of therapies, and will develop a framework in which
these applications can compete more effectively for funding. We
expect this program to be initiated in early fiscal year 2003.
--Participants also encouraged NIH to increase our understanding of
how PD affects the dopamine systems of the brain. For years,
NINDS-funded researchers and our own intramural scientists have
been engaged in this work, primarily through basic science
approaches to understanding the fundamental malfunctions in
dopamine neurons that lead to their degeneration. We will
continue to support this research, through investigator-
initiated awards, as well as special solicitations and
workshops, as critical new areas of biology are identified.
--To complement these efforts, participants recommended further
expansion of research beyond the dopamine systems of the brain.
This would include other brain systems and circuits that may be
affected by PD, the effects of PD throughout the body, and the
resulting non-motor complications of PD--which can range from
depression and sleep disturbances to speech problems. NINDS is
committed to supporting many aspects of this research,
including continued exploration of the damage to sympathetic
neurons caused by PD. An expansion of this work in all relevant
research areas will likely require a trans-NIH effort.
--Despite the wide use of validated scales to assess outcomes, both
NINDS and PD researchers in general have recognized the need
for better biomarkers--biological indicators/tests of disease
susceptibility, progression, or response to treatment.
Certainly, our continued focus on the genetics of PD will lead
to new ways to assess individual disease risk. However, early
biomarkers of this risk and later markers of progression may be
much more difficult to develop. NINDS will continue to fund
improvements in imaging and other currently used techniques;
however, the central problem in identifying new markers is our
incomplete understanding of the disease process at the cellular
level. For example, researchers in the Alzheimer's disease
community understand how specific molecules are broken down in
affected neurons--this offers hope for finding some of these
molecules in the spinal fluid or blood. However, researchers
have not fully characterized the degradation processes that
take place in neurons affected by PD, and thus, we do not know
if evidence of these processes can be detected peripherally.
NINDS staff is acutely aware of these difficulties, and will
continue to evaluate mechanisms that can enhance and accelerate
this research.
--Participants also recommended NIH support for preclinical studies
of gene therapy, so that this research can move forward into
clinical testing. We have already solicited applications on
this therapy, and we expect that our efforts in encouraging
translational research will also help in this regard. Further,
once clinical studies are developed, we anticipate that the
framework we have already developed in our clinical trials
program, and our enhanced communications with the FDA, will
facilitate the development of gene therapy approaches in PD.
--Lastly, the group recommended that NIH support improvements in
animal models of PD, including small animals and non-human
primates. We are already deeply invested in this work, and NIH-
funded investigators have developed new animal models of PD
since the start of the Agenda. However, we are committed to
improvements in these models, and as a first step in the
process, we have already engaged the extramural research
community in discussions of how to facilitate the sharing of
models that are currently available.
In the past two years, we have been successful in using the PD
Research Agenda to guide our support of Parkinson's research, and this
strategy has helped us to achieve the balance of investments outlined
in the original Agenda. NIH estimates that PD research funding will be
approximately $199 million in fiscal year 2002 and $215 million in
fiscal year 2003. We believe that sufficient resources will be
available to support the PD Agenda during this period, while NIH also
attends to its many competing priorities. We will use both the
recommendations from the original Agenda and those identified at the
January and subsequent consortia meetings to guide the allocation of
our resources in different areas of PD research.
We recognize that the Congress and the Parkinson's community have
concerns about the level of funding that NIH has been providing for the
implementation of the Agenda. Appropriations for NIH and its individual
ICs have been extremely generous in past years, and Parkinson's
research has clearly benefitted from this generosity. As a result,
NINDS invested more of its fiscal year 2001 funds on PD research than
on any other disorder except stroke, which has an incidence at least
ten-fold higher than that of PD. However, workshops and planning
efforts increasingly indicate that opportunities for research advances
against problems such as stroke, epilepsy, multiple sclerosis, brain
tumors, autism, spinal cord injury, muscular dystrophy and health
disparities are abundant. Maintaining an appropriate balance among the
many disorders within the NINDS mission is a challenge as the Institute
moves toward the future. One hopeful note is that basic research
applies to many disorders, and even research focused on a particular
disease, has a bearing on many others. NINDS must capitalize on these
synergies to most effectively carry out its mission in the coming
years.
In closing, we are extremely proud of the progress we have made in
accelerating research in Parkinson's disease, and we are grateful for
the support of the Congress in these efforts. We do not have a cure
yet, but we are initiating clinical trials that we believe will be
critical to improving the treatment and quality of life of individuals
with PD; we are developing a framework so that basic research can be
effectively translated into treatments; and we continue to invest in
essential basic science research--the foundation for all progress in
medical science. We are not alone in these efforts. Many other ICs at
NIH are involved in the implementation of the PD Research Agenda, and
several voluntary organizations have expressed an interest in further
collaborations. We will continue to work with other ICs through the NIH
Parkinson's Disease Coordinating Committee, and with our external
advisors and colleagues from the research and voluntary communities
through the Parkinson's Disease Implementation Committee. With all NIH
ICs and voluntary organizations working together, this undertaking can
and will be successful.
Thank you, Mr. Chairman, for the opportunity to speak with you
today. I would be happy to answer any questions.
Senator Harkin. Thank you very much, Dr. Penn. We will go
down through all the witnesses, and then we will come back for
questions.
Next we have Dr. Ole Isacson, Director of the Center of
Neuroregeneration Research and the Udall Parkinson's Disease
Research Center at McLean Hospital at Harvard Medical School.
Dr. Isacson is now an associate professor of neurology at the
Harvard Medical School. Dr. Isacson, welcome.
STATEMENT OF DR. OLE ISACSON, DIRECTOR, CENTER ON
NEUROREGENERATION RESEARCH, McLEAN HOSPITAL
AND HARVARD MEDICAL SCHOOL
Dr. Isacson. I want to thank you for inviting me and for
your leadership on this issue. First of all, I would like to
tell you that I am also very honored to speak about the
exciting science that is possible through the work and the
effort at the NIH. Beyond our science, it is also a human
effort in that there is also a wonderful team spirit on this
where the science has reached a level where we can actually
make an implementation of a research agenda as Dr. Penn just
mentioned.
With your permission, Mr. Chairman, I would like to use
this chart to show some of the work on science that relates to
this.
Herein lies the problem. This is the part of the brain that
is called the midbrain, and in this part of the region here,
about an inch across, you have something called the substantia
nigra. Here you have the famous dopamine cells that everybody
talks about that die in the disease. So, we have a few million
here among trillions of nerve cells. The process of Parkinson's
disease affects most of the brain, but only these cells here
seem to be vulnerable. When you lose them, you get Parkinson's
disease.
So, obviously from a very common sense perspective, you
realize, as Dr. Penn mentioned, that preventing this
degeneration, reactivating the cells, or replacing them is a
very reasonable strategy. And I will show you in a couple of
minutes here that that can be done.
So, this is what we teach at Harvard. So, what I am showing
the Senators now is a drawing of how the brain works. It is
known as a synapse, this thing here.
If you remember the million cells in the midbrain, each one
of them sends about a thousand of these very microscopically
small, less than we could ever see without a microscope, up in
the front of the brain. They are these terminals where that
release the dopamine. The Nobel Prize last year was awarded for
people who understood that when you lose the dopamine here, you
can take a drug L-dopa that gets accumulated here and sent out
here into this brain region.
This is a very sophisticated element, and we scientists are
trying to restore that one, and we are using every effort we
can, all the scientific efforts we can, to restore this unit
here. Most of the drugs that you currently can take as a
patient relate to the understanding of this. But there are a
number of new opportunities in restoring the function here,
activating this element with growth factors, for example, which
may become a home run, or any other analogy you want to choose,
for Parkinson's patients.
This next shows the mechanism. As Dr. Penn mentioned, there
are gene defects, the way the cell works, its energy metabolism
called mitochondria, the proteins that were mentioned, the way
they mess up the dopamine neurons and the way that leads to
dysfunction of that particular cell. At each of these phases
listed on this panel here, there are research advances. What we
feel as scientists is we now need to translate those, make them
real for the patients, and aggressively move forward to
organize the scientific efforts.
There are many ways to organize that. This scientific chart
here or this strategy here shows you some of these novel
therapeutic approaches. They include what we call biomarkers.
We need to be able to look at the brain and see what is
happening both during the disease process and when we try
restorative therapies. We are trying to prevent the disease as
I mentioned previously, trying to keep the brain working, also
replacing the cells, and also as was mentioned previously, we
are using stem cells. This country is very well known--I am
actually an immigrant--all over the world for its innovation
and attention to discovery. We need a free science to be able
to find the necessary treatments for Parkinson's disease, both
using stem cells, understanding gene biology, and aging.
So, finally, to give you some evidence of that, thanks to
the NIH Udall Center, the Udall bill, my team in Boston managed
to translate some of these findings from stem cells into an
experimental model of Parkinson's disease. What you see here on
this panel is an imaging on the left side, but on the right
side here you see implantation of mouse embryonic stem cells,
and these stems cells differentiate into to the dopamine neuron
that I told you was the core of the problem. So, in a prototype
manner, we are already able to show in the laboratory that we
have ways of obtaining the cell that dies in Parkinson's
disease. Obviously these are prototypes, which means just like
a new airplane or any new discovery, that we need a lot of work
to move these things forward, and I look forward to describing
some of the organizational methods, management that maybe can
accomplish that.
So, if I may wrap up here, some of these concrete
scientific studies do not only pertain to Parkinson's disease.
Parkinson's disease, for reasons of its scientific promise, has
spearheaded many other discoveries. When we make breakthroughs
for Parkinson's disease, it is very likely that we will also
make breakthroughs for ALS, Alzheimer's disease, and spinal
cord degeneration. So, Parkinson's disease research is a way of
opening doors to new therapies. Therefore, I feel very
strongly--and most scientists and doctors feel the same way--
that there is a real need to focus on this disease and do
everything we can possibly to help and cure patients with
Parkinson's disease.
PREPARED STATEMENT
This shared purpose we also feel with you as the Government
and giving us the opportunity to do the research.
I would like to end my testimony there. If you have any
further questions.
[The statement follows:]
Prepared Statement of Dr. Ole Isacson
Senator Harkin and members of the committee, I am Ole Isacson,
Director of the Neuroregeneration Laboratory, McLean Hospital and
Harvard Medical School, and the NIH/NINDS funded Udall Parkinson's
Disease Research Center of Excellence. The research center I direct is
dedicated to basic research on the prevention and treatment of
Parkinson's disease and neurodegenerative diseases. For Parkinson's
disease, we have developed models for new treatments with cell
replacement and transplantation of embryonic stem cells. We have shown
that we can reduce parkinsonism in several experimental models that I
will describe to you. In particular, I would like to emphasize that
over the last few years with the available Udall bill, the activities
that these centers have created throughout the United States, and there
are 11 of them, is considerable. The work on Parkinson's disease
treatments and possibly cures is an achievable goal with effort placed
in science and medicine. It is my opinion that there is an opportunity
to increase the funding for Parkinson's disease research to reach the
next technological level, which would include treatments. A strong
research effort can be funded further to grow research centers and to
grow national core facilities to provide service to smaller research
groups across the nation and internationally to reach their scientific
and therapeutic goals for Parkinson's disease faster. In particular, by
building such an effort, we will increase the capacity not only for
achieving treatments for Parkinson's disease, but there will be several
measurable and meaningful results for the treatments of
neurodegenerative diseases such as Alzheimer's, Huntington's and
Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig's disease), to mention a
few, as well as spinal cord damage.
One of the most successful drug therapies for any neurological
disease is L-dopa for Parkinson's disease. This was made possible
primarily through the insights of scientists and clinicians, who in the
late 50s and early 60s used the information obtained from animal and
pathological studies to provide patients with a treatment. My
laboratory's approach for Parkinson's disease is based on the idea that
the degenerated dopamine neurons can no longer provide synapses in
which the drug (L-dopa) can be converted and released in regular
amounts into the striatum, where dopamine receptors translate this into
neuronal firing and activation of the striatum. L-dopa and dopamine
analogues, while initially helpful, eventually become insufficient with
debilitating side effects for the patient. Since this loss of efficacy
is likely due to continued loss of synaptic control, the homeostatic
mechanism of transmitter release, the reinnervation with synapses by
implanted or regenerated dopamine neurons can potentially provide a
better intervention than drugs alone. Many practical issues remain
before it becomes a standard and reliable therapy. Hopefully,
scientific insights about new donor cell sources, as are described
here, their axonal integration and connections will provide patients
with a useful therapy. Clearly, it is necessary for these scientific
discoveries to be matched by technical developments in neurosurgery to
achieve that translation into useful clinical practice. Rapid progress
seen in developmental biology, molecular biology, as well as technical
developments of neurosurgery can further accelerate achieving
regeneration and repair for a large number of neurological patients in
need.
Typically, without any pharmacological treatment, a person
afflicted with Parkinson's has a stiff posture and slightly unstable
gait, with the arms trembling. In addition, many with Parkinson's
disease experience emotional difficulties in dealing with the disease,
but do not feel that their minds are otherwise affected. The
instability in their posture, the masked face, the gait disturbance,
the speech disturbance and the poor dexterity are very incapacitating.
This type of patient was first described coherently by James Parkinson
(1755-1824) in an essay ``On the Shaking Palsy'' (1817, Sherwood, Heely
and Jones, London, England). In the United States alone, there are now
at least a million Parkinson patients, and approximately 1-2 percent of
persons above age 65 will get the disease. Nationwide, drug therapy
alone costs about $6 billion per year and the cost of hospital care and
other consequences associated with a person having Parkinson's disease
are estimated at $25-50 billion per year.
Like Alzheimer's disease, Parkinson's is a disease that may happen
in younger people, but the risk increases dramatically with age. This
is probably because many of the cellular systems in the brain are
difficult to renew or regenerate by themselves. While there are
trillions of nerve cells in the brain, when nerve cells start
degenerating as we get older it becomes harder and harder for the brain
to compensate for the loss of these cells. For instance, in Parkinson's
disease the symptoms are caused by the selective loss of a relatively
small population in the brain consisting of approximately 500,000
dopaminergic cells. They are situated deep in the midbrain in a place
called the substantia nigra, literally the black substance, caused by
melanin seen in those neurons. In any brain that grows older, some of
these dopaminergic neurons will dysfunction over time. The rate at
which they die or dysfunction is individual. For certain people, whose
rate of dopaminergic cell loss is slightly higher than normal, the
likelihood that they will eventually lose the critical 85-90 percent of
the cells that are needed for normal function is high. The brain
somehow manages to compensate for a loss of about 85 percent of these
cells, but when only a small number of functional dopamine cells or
less remain on each side of the brain, the symptoms of Parkinson's
disease appear. The neurotransmission that takes place at the nerve
terminals that produce dopamine is necessary for all of us to initiate
movements and without it, we freeze up and become unable to move.
The pharmacological substitution therapy provided by L-dopa
revolutionized the treatment of Parkinson's disease. The neurosurgical
treatment (pallidotomy) now became uninteresting to many clinicians, as
it was hoped that L-dopa was a sufficient treatment for Parkinson's
disease, and moreover, that this type of pharmacological substitution
would be possible for all of the other neurodegenerative diseases. It
turned out that the solution wasn't so simple. After 5 to 10 to even 15
years of treatment, the L-dopa became less effective, and not in the
manner of normal drug-induced tolerance. As is now well known, the
patients experienced severe fluctuations in the drug effect, despite
relatively constant levels of the drug in the blood and the brain. The
so-called ``OFF'' phenomenon describes a time when the drug somehow
becomes ineffective for the patient. At such times, the patient freezes
up momentarily and loses mobility. The ``ON'' times are when the drug
works and the patient gains mobility. However, both the ``ON'' and''
OFF'' times may be adverse. Symptoms can fluctuate wildly with L-dopa
treatment or analog drugs. During ``OFF'', freezing and rigidity and
inability to initiate movement is then further compounded by side
effects during ``ON'', such as extra, involuntary movements generated
by the drug. These hyperactive movements and dystonia (abnormal muscle
tension and postures) are debilitating. Given that these ``ON-OFF''
phenomena appear earlier and more prominently in patients with
chemically induced Parkinsonism (such as due to MPTP toxicity), it
seems probable that the more severe the damage to the dopamine system,
the less likely it is that systemic drug delivery (oral administration
of drugs, for instance) will be effective. Moreover, it is reasonable
to assume that one of the reasons L-dopa becomes less effective is that
it cannot be taken up by the decreased number of surviving dopaminergic
neurons to create some form of regulated release of the transmitter.
This has led a number of scientists to question whether
pharmacological drug substitution therapy will be effective for the
age-related neurodegenerative diseases. If synaptic control and
regulated release of a single substance is needed, then we may have to
deal with the more complex issue of trying to re-create synaptic
networks and/or preserve them from degeneration. Since the ``ON-OFF''
phenomena in Parkinson's disease are so debilitating, some
neurosurgeons and neurologists found it worthwhile to explore
pallidotomy once again in the 1990s. More recently, electrical
stimulation of the subthalamic nucleus (DBS) has been shown to
alleviate some of the movement disorder of Parkinson's disease. Another
procedure, ``thalamotomy'', surgically removes a subset of neurons in
the thalamus that participates in the parkinsonian tremor. Like all
experimental methods, there is the need for an extensive evaluation of
the effects.
In addition to the L-dopa or dopamine agonist drugs previously
mentioned, and the neurosurgical treatment methods, there are a number
of research efforts to prevent or treat Parkinson's disease. Some
centers are involved in locating so-called susceptibility genes for
Parkinson's disease. Although there seems to only be a small proportion
of Parkinson's patients with a genetic component, certain genes may
make it more likely to develop Parkinson's disease. If the disease is
multifactorial, susceptibility genes may lower the threshold for
developing the disease. Some scientists also indicate that there may be
a heterogeneity among susceptibility genes, such that different
genotypes may develop the same Parkinsonism. And as we have previously
discussed, the disease is age-linked and therefore a number of
biochemical changes occurring naturally by age may interact with the
genes at various times. Such genetic research, in combination with new
methods in molecular biology, may give us tools to develop preventive
treatments.
As previously discussed, when dopamine is so severely reduced in
the caudate putamen that Parkinsonism appears, we can give patients a
precursor of dopamine, L-dopa, to reverse some of the loss of dopamine
in the brain. This was first reported by Birkmayer and Hornykiewicz
(Wien Klin. Wochenschr. 73, 787-788, 1961). Along with the discovery
that L-dopa substitution worked in the early phases of Parkinsonism,
the last 35 years of neurological research has provided us with a
number of drugs that can either mimic the action of dopamine (analogs/
agonists), block its uptake from the synapse (re-uptake blockers) and
stimulate its release or inhibit its metabolic removal. In addition,
other neurotransmitter-related drugs that interact with dopamine in the
caudate and putamen have been used. The outstanding discovery that the
precursor to dopamine (L-dopa) will provide symptomatic relief for
patients with Parkinsonism still remains with some minor modifications,
the major drug treatment for patients. However, the fact that this drug
and other similar drugs lose their effectiveness over time still
remains the major problem with Parkinson's disease. It is unclear at
this time whether optimization of the dopamine agonist effects can
provide an effective long-term treatment for Parkinsonism, even if new
receptor agonists are developed. The question therefore remains whether
it will be necessary with synaptic replacement in the striatum to
reverse the course of advanced Parkinsonism.
In cell culture and animal studies, it has been shown that brain-
derived neurotrophic factor (BDNF) can help dopaminergic neurons
against toxic insults. Similar effects have been obtained by infusions
and increased supply of glial-derived neurotrophic factors (GDNF) by
somatic gene therapy. If research is directed towards appropriate
delivery of such substances to patients at risk for developing
Parkinsonism or patients with accelerated cell loss in the substantia
nigra, it is likely that some benefits could be derived. Moreover, by
this kind of research we may find other substances that could mimic the
effect of trophic factors and therefore help prevent the degeneration
in the substantia nigra and other vulnerable brain regions. It is my
overall impression that basic neurobiological research towards
understanding the mechanism involved in neuronal death, and of
dopaminergic neuronal death in particular, are well-underway and very
focused. It is likely that these studies will yield sufficient insight
to develop new clinical therapies. A word of caution in this regard,
though, is that while clinical trials may be initiated, it could be
some time before they are refined so that they can be available to a
large number of Parkinson's patients.
The evolving science and therapies for brain disorders may develop
in parallel with insights about the brain's own capacity for repair. In
fact, the brain is probably the most adaptive organ at a structural
level for continuous change and signaling, as well as morphological
adaptation to functional demand. I am therefore convinced and very
optimistic that new technologies and therapies can be developed through
scientific research to cure Parkinson's disease. A national effort and
increased funding for such work would provide the stimulus to take
advantage of these unique opportunities at this time.
Senator Harkin. Thank you very much, Dr. Isacson.
Now we turn to the driving force behind almost all of this,
Joan Samuelson, president and founder of the Parkinson's Action
Network.
A lawyer for many years, she was diagnosed with Parkinson's
in 1987. Mrs. Samuelson has testified before this subcommittee
more than 10 times, and we are proud and privileged to have you
back again. Please proceed.
STATEMENT OF JOAN SAMUELSON, FOUNDER AND PRESIDENT,
PARKINSON'S ACTION NETWORK
Ms. Samuelson. Thank you so much from the bottom of my
heart, Mr. Chairman, Senator Specter. Your visionary leadership
on this subject has benefitted our community of a million
Americans with Parkinson's disease beyond measure, and giving
us the opportunity to be heard and the work you have done to
help our cause we are deeply grateful for beyond anything I can
describe, and thank you so very much.
My testimony today I see as a story of hope. It is about
hope that is essential, and it is a story about failed hope in
the past and hope that we hope will be able to be realized in
the future and should be. Hope is an ingredient that, to
someone who has been diagnosed with Parkinson's disease, is as
essential as food to continue living.
When you walk out of a doctor's office with a diagnosis of
Parkinson's disease, your foundation has been taken from you
because you are told you have a progressive, degenerative,
chronic motor disorder that will only get worse. But there is
wonderful medication that now will enable us miraculously to
walk into a room and testify and drive our cars and work in the
world and live with dignity.
But we also are told that those cells are continuing to
die, as Dr. Penn said, 75 to 80 percent of them are already
gone, and that cell death and cell shutting-down is continuing
relentlessly and that there is no solution to that right now.
What that means is we have a disease for which we cannot
hope that we are going to outlive the odds, that we are going
to beat the odds because there are not any odds to beat. There
is not such a thing as remission. There is not such a thing as
perhaps some combination of chemo and radiation that causes us
to be labeled a survivor and be able to march in parades with
that label. We know that we are going to eventually become
prisoners of our bodies, unable to move and speak and swallow
and die before our time. And yes, Parkinson's does kill.
So, what we have to do is cling to what is raw hope. What
we have now, as Dr. Penn and Dr. Isacson were describing and as
we heard in the scientific briefing at our public policy forum
yesterday, is that our hope is now a verifiable expectation.
Parkinson's is no longer called incurable. It is curable. What
that means for us is that we can hope with something more
concrete, but what we need is for that hope to be realistically
matched with the opportunity to realize the scientific results
from the promise that these scientists have been describing.
And therein lies the dilemma that I want to talk about.
My testimony needs to be, I think, a bit of a report card.
In 1999, we had the tremendous honor, Michael and I, of
testifying before this committee, and at that point scientific
promise was great and on the basis of that and on the basis of
that hearing and your leadership, the scientists in the country
involved in Parkinson's research teamed up with the National
Institutes of Health and created the Parkinson's Disease
Research Agenda, an historic document that laid out a road map
to realize that promise and that hope with a cure, with some
curative therapy that would rescue these million Americans or
as many of us as the science could realistically rescue with
enough money. And so, the science was laid out and a price tag
was put on it of $1 billion over 5 years. And the clock began
to run.
That research agenda was set in the year 2000, and as this
committee knows so well and as we have come back to you and
discussed it, it has not been funded. There are scientists that
come to us and speak to our gatherings and describe the
enormous promise, but their extreme frustration with the work
that could be done that is not being done. The consequences of
that are great and real and human.
What it means is that we have people for whom hope is
fading. We cannot take care of those for whom hope has died,
and we have lost people in the 3 years since 1999 and it
grieves us. The father of our advocacy director, Lynn Phillips
from Mississippi, many people who are gone or who are
completely prisoners of their bodies. And hope is fading
terribly for people like Milly Kondracke who sits behind me.
We should try to save Milly. It may not be possible
scientifically, but it could. And we must try, it seems to me,
as a country if we have that potential. And there are many
others for whom hope is still there and it is strong, but we
know we are in trouble.
Three years ago I described going to see Mo Udall and that
being my future. I am still doing well, relatively, for 16
years post-diagnosis, and I am so deeply grateful for that, but
I wake up every morning just about as frozen as he was when I
went to see him. And some day that pill I take will not work,
and that day may be soon. And I so desperately want, as every
one of these other people in this audience and the rest of the
million Americans, our country to make the investment that it
must because the science is there to benefit not just us, but
people with the other disorders that Dr. Isacson described.
PREPARED STATEMENT
We know it is a difficult problem, but we believe that with
the leadership of the Congress, working with the National
Institutes of Health, that the money is there and that it must
be spent because hope is real and realistic now. Given that, it
would be a crime to let it fade.
So, thank you for your leadership and your vision. I just
ask that we work together on this next difficult but doable
step. Thank you.
[The statement follows:]
Prepared Statement of Joan I. Samuelson
My testimony must begin with our thanks on behalf of the entire
Parkinson's community to this Committee, for this hearing, for the
opportunity to be heard, and for your leadership on our behalf. We are
deeply grateful to Chairman Harkin, Senator Specter and the members of
the Committee to help ensure that this dreadful disease is conquered as
soon as humanly possible.
I also would like to recognize several members of the audience who
have gone to great lengths to be here. First, joining us today are
three former Senators who have Parkinson's disease, the Honorable
Claiborne Pell (D-RI), Brock Adams (D-WA) and Charles Mathias (R-MD).
Also joining us today is Mrs. Carolyn Long, wife of Former Senator
Russell Long (D-LA), who also has Parkinson's. I know they share our
message today.
Also present are Lynn Fielder from Palo Alto, California, and her
nine year-old daughter, Maya. Maya recently wrote Senator Harkin,
explaining how her mother's life may depend on an increased federal
commitment for Parkinson's research. Her letter will appear in the
Congressional Record today. Thank you all for being here.
I seek to persuade this Committee of three things. First, the cost
of Parkinson's--human, financial and otherwise--is too great to endure.
Second, it is now possible to take concrete steps to stop it. Third,
that it requires the federal government to honor a commitment made two
years ago, to fund development of a cure thoroughly and aggressively.
So there are many reasons for our plea to you today. Our message
today is one of huge human suffering, dazzling scientific promise--and
a failure of our government to translate that promise quickly. It is
inexpressibly sad, but true. Parkinson's is waging a war in the brains
of the million of us diagnosed, and the several million more Baby
Boomers and others who have pre-symptomatic dopamine cell loss. This
war will take an unacceptable number of victims. We have weapons
sitting in the warehouse. And--by government choice--we are meandering
to a cure.
This is, in a way, a progress report, given almost three years
after our first report to this Committee in September 1999. It is a
hard thing to do for two reasons. First, it requires that we tell tales
of the failure of hope. That goes against every instinct of those of us
diagnosed with a chronic progressive disorder of this magnitude: with
such news, the only way to go on living is to keep our spirits alive,
which requires hope--the food on which the spirit feeds. So, we believe
the cure will come--in time for each of us.
The brutal reality of Parkinson's degeneration, however, is that as
more and more dopamine neurons shut down, we require more and more
dramatic rescues, until the day when the system utterly fails to work.
At that point, we are forced to recognize that hope is gone and give up
our personal dream in favor of those with more time. In the three years
since the 1999 hearing, I have watched hope fade in that way for many
people. It is always a cruel thing to watch; sometimes it is lethal.
Take Lynn Phillips of Mississippi. He tried every experimental
program, including a deep brain stimulation procedure that required his
town to throw a huge chicken fundraiser to pay for it. But finally,
Parkinson's won: the death certificate presumably refers to
complications secondary to his Parkinson's--but Parkinson's had so
beaten him up that he had few defenses left.
And take Fred Zeiss of New York City, who was forced in recent
years to put aside his career, and in his depression put on 100 pounds.
It was the resulting heart attack that killed him, but his family says
it was really Parkinson's.
Our office was hit hard this past year by Parkinson's deaths to the
father of our Advocacy Director, John Rogers, who died last fall after
brutal suffering; and the uncle of our Executive Director, Elisabeth
Bresee Brittin, last winter. There are many others across the country,
most of whom have not died, but live lives robbed of nearly every
freedom they possess short of the freedom to think and dream. The
stiffness and slowness of movement combine to cause the body to freeze
up. At that point, the mind is encased as if in an iron lung, by an
unyielding outer shell. That shell is us, though: the body is
imprisoning itself. In those cases, it feels just about as cruel to
watch them continue to live.
When I was diagnosed, I decided that I would never succumb to such
a state. I still hold a profound belief that I will be rescued in time
to keep my livelihood, my independence and dignity. But I have to admit
that, more frequently than three years ago, I experience episodes of
that final stage--when the available medications work poorly at best.
So where are we in fulfilling the desperate hope of a million
Americans, and the approaching need of millions more? The science is
full of promise: There is a dazzling set of cutting-edge biomedical
approaches waiting to be applied. They include:
--High throughput screening of possible toxic agents and therapeutic
compounds;
--Gene-environment initiatives using high tech testing;
--Applying information on proteins involved in Parkinson's genetics
to understand the disease process;
--Imaging advances for earlier diagnoses before symptoms appear;
--Neuroprotection: applying all these advances to prevent cell loss
in the healthy and protect those afflicted against further
deterioration.
And, for the million-plus of us who need a therapeutic rescue,
there is an equally dazzling array of new approaches:
--Cell restoration
--Cell replacement
--Gene therapy
--Viral vector technology
--Cell line creation technology, using techniques such as stem cells
The science of Parkinson's is at the front lines in all these
areas. Eminent scientists are so optimistic that for years they have
been predicting and quantifying the time remaining--highly unusual, and
hopeful, behavior.
But precious little concrete movement toward completion of some
curative treatment has occurred. It is not the fault of science. It is
a failure of government to act. This is the second piece of the report
that it hurts to tell.
I hasten to add that I do not fault this Subcommittee. It in
particular has frequently expressed its concern and led initiatives
that support Parkinson's research. In response to Congressional
urgings, in 2000 the NIH convened a team of Parkinson's researchers who
developed the Parkinson's Disease Research Agenda--a plan that called
for a $1 billion additional investment in Parkinson's research over
five years. Since the Agenda's development, the Congress--and
especially this Committee--has urged the NIH in increasingly strong
language to fully fund the Research Agenda. Every element for success
seemed to be in place, including the process of ``doubling'' the NIH's
overall budget by 2003, to ensure that a Parkinson's increase would not
come at the expense of other disorders.
Despite these efforts, the federal commitment for Parkinson's is
falling far short of the Agenda's targets. While each month brings
further progress and new discoveries that could lead to a Parkinson's
cure, the percentage of spending on Parkinson's research has not even
kept up with overall NIH spending. In fact, in the two years since the
Agenda was completed, there already is a $100 million shortfall in the
NIH's spending on Parkinson's research. The numbers create problems in
funding that we hear constant stories about: the many grant applicants
with great ideas and high peer review scores, but where low funding
scores kept them below the pay line.
At the root of the problem is an utter failure of leadership to
implement a research agenda for Parkinson's. Despite some very hard
working and wonderful scientists at lower levels, there has been an
absence of vision and commitment at the top--of both the NIH and the
key brain-related institute--which manifests in many ways. Despite huge
opportunity for major strides in brain research, the NINDS directorship
has been a revolving door for years. The institute's lack of focus and
direction has discouraged good candidates. The NIH hierarchy seems to
regard the Parkinson's Disease Research Agenda as nothing more than a
distant aspiration rather than an operational document that must be
funded. However, scientific directors cannot make this happen without
budgetary and policy commitments from the top. This situation is,
without question, having the effect of delaying a Parkinson's cure.
For all these reasons, the road to a Parkinson's cure is a
meandering one, with huge consequences. First and foremost, people with
Parkinson's will suffer. That is simply not right. Americans with other
disorders that seemed intractable--AIDS and cancer, for example--are
alive because of the benefits of federal research investments. It
should be Parkinson's turn. Moreover, the scientific and bio-
technological advances that result unquestionably will speed
breakthroughs in many other disorders.
So what is to be done? The Congress cannot allow this un-met
promise to continue. We urge this Committee and the rest of Congress to
use every available power to turn this around quickly. We urge the
following:
--That the NIH Director use his transfer authority to commit $50
million for Parkinson's research this year;
--Full funding of the $197.4 million increase over the baseline year
for 2003, year three of the NIH's five-year Parkinson's Disease
Research Agenda, including significant funding of translational
and clinical research;
--Complete the five-year doubling of the NIH's budget by providing
$3.7 billion (for a total of $27.3 billion) in fiscal year
2003;
--Continue and expand the NIEHS budget, with an increase of $30
million in fiscal year 2003 for Parkinson's focused research;
--Work closely with the NIH to ensure that they aggressively
implement the Parkinson's Disease Research Agenda.
It is the responsibility of the federal government to seize this
opportunity and that of Congress to ensure that they do, including that
the NIH be responsive to Congressional report language regarding
Parkinson's funding. That's why your leadership is critical to ensure
that the visionary Parkinson's Disease Research Agenda is regarded as
an operational document that must be fully funded and implemented,
rather than merely an aspirational document that is never truly
realized.
We fear that we already have missed the opportunity to save some
people by failing to fully fund the great scientific potential. But, if
we act now, there are many others who can still be saved. With this
Subcommittee's leadership, the future we dread will be rewritten into a
history in which Parkinson's has been sidelined forever. That day can't
come too fast.
Senator Harkin. Thank you very much, Joan.
Don Schneider lives in Clinton, Iowa. That is on the
Mississippi River, for those of you who do not know. It is the
same town where he was born. He worked at radio station KROS
for most of his career, eventually rising to general manager of
the station, and President of the Iowa Radio Network, before
Parkinson's disease forced him to retire 3 years ago. He is
accompanied here by his wife, Rita.
Don, thank you for being here. As I said, your statement
will be made a part of the record in its entirety. If you could
just sort of sum up what you want us to know about how this has
affected you and what you want us to do. Please proceed.
STATEMENT OF DON SCHNEIDER, PARKINSON'S PATIENT,
CLINTON, IA
Mr. Schneider. Well, I would first like to say for an Iowa
farm boy who was standing in a hayfield on Sunday, it is pretty
overwhelming to be here in front of these bright lights and on
this panel with these great personalities. In fact, I kind of
feel as out of place as a faithful husband on an edition of As
the World Turns.
But anyway, I guess I am here to put a human face on
Parkinson's disease, and I figure Muhammad is providing the
pretty face, so you will just have to put up with mine.
Fifteen years after my diagnosis, Parkinson's disease is
continuing to slowly but surely chip away at my quality of
life. It has forced me to leave a job I loved, placed a heavy
financial burden on my family, and at times each day leaves me
unable to walk, read a book, or even dress myself. For someone
raised as an independent farm boy, I cannot express the
frustration that accompanies this type of disability.
As the Senator mentioned, I come from Clinton, Iowa. After
graduating from high school, I attended radio school at Brown
Institute in Minneapolis, and at the age of 19, started as a
night announcer on a small radio station in Clinton, Iowa. I
served in a number of capacities with that station, everything
from an announcer to program director. In 1987, I purchased
stock in the company and was named general manager.
Professionally I was active in the Iowa Broadcasters
Association and, as the Senator mentioned, President of the
Iowa Radio Network. I was also active in my local community as
every small businessman is. I was a member of the Kiwanis Club,
helped the United Way board of directors, served on the
Substance Abuse Council, and was part of countless fund raisers
for many worthwhile projects in the Clinton area.
I enjoyed working with young people. I was inducted into
the Junior Achievement Hall of Fame for serving as an applied
economics advisor. I coached junior football and basketball.
Later I even took up the stripes as a high school basketball
official.
It was in 1988, during a high school basketball game I was
refereeing, when I held out my hand to indicate two shots, I
noticed an uncontrollable shaking. Well, my family had also
begun to notice a blank stare on my face, and I was
experiencing slowness of movement and pain in my neck. One
visit to the clinic and I was diagnosed with Parkinson's
disease at the age of 35. For 5 years after my diagnosis, I hid
it from all but my family. When people asked, I would simply
say I had a neurologic disorder. As Michael Fox put it, you do
not want to believe this is happening to you and you certainly
do not want anyone else to know what is happening to you. You
worry about what they will think, how they will treat you. It
was extremely difficult, after being someone who was always in
charge, to be forced to depend on others to help me.
At first, with the help of my medications, I continued
living a relatively normal life, and as long as the medication
was working, I could do just about anything. But eventually the
progression of the disease and side effects of the medication
left me no longer able to be fully functional at work, and my
condition worsened to the point that I had to end my broadcast
career and retire from the station in 1999.
Today I reside in rural Clinton County with our three
youngest children. My two older children are now finished with
school and living on their own. Katie, 21, is serving our
country in the U.S. Army stationed at Fort Polk, Louisiana. My
other daughter, the oldest, Sarah, graduated from the
University of Iowa Hospitals and Clinics and is working as a
registered nurse in the Neurology Department.
This is not to say that it has been easy. I can recall many
profound sadnesses that I saw in the eyes of my family after
the diagnosis and we all faced the uncertainty of what will
happen in the future. I cannot deny that each day I worry about
what the future will be like. On one hand, I know there has
been great progress made. There are new medications that have
become available just in the 15 years that I have had
Parkinson's disease. But there is still no known cause and the
possibility of being trapped with an active, alert mind in a
body you cannot control is a fate worse than death.
Since giving up my job, we have had to rely on my wife's
income in an accounting firm and Social Security disability to
get by. Fortunately, my wife makes a good living, but it has
taken an economic toll on our family. We are facing the
prospect of soon losing our health insurance with its
prescription drug coverage. With a cost of over $700 a month
for my prescriptions, this will certainly make us have to do
with a lot less.
I often think about all my family has been missing and had
to give up because of my diagnosis and condition with
Parkinson's disease, and I have tried to channel some of that
anger into the work I have done with a local support group in
Clinton, Iowa. Our group of over 30 families has been a great
help to me in facing the daily struggles of Parkinson's.
No one knows why or how I got this terrible disease. Is it
genetic? Well, two of my great uncles did have Parkinson's
disease, but one was on the maternal, the other on the paternal
side. Does the environment play a role? I grew up drinking farm
well water, but so did the rest of my family and none of them
has Parkinson's. The bottom line seems to be we just do not
know what causes this disease, but I am hopeful that we will
have the answers soon.
I am not a quitter and I refuse to give up hope. I have
always had a love of old cars. In fact, I keep a red Corvette
in my garage at home right now. One of my mottos that I have
tried to use all the time, dealing with Parkinson's disease, I
stole from a movie called The Gumball Rally. As the race in
that movie is about to start, a driver in a Ferrari turns to
his co-pilot, tears off the review mirror, and says, ``now the
first rule of Italian driving--what's behind me does not
matter.''
I do try to keep looking ahead rather than worrying about
what is behind me and remembering all that I have lost, trying
to be thankful instead for my wonderful family and all that I
have going for me.
PREPARED STATEMENT
Again, I thank you, Senator Harkin, and I am especially
proud as an Iowan of your being awarded a second Mo Udall Award
last night for your work for fighting against Parkinson's
disease. And as The Champ might put it, with the help of all
these great people, I cannot see how we will not whip this
thing sooner or later. Thank you.
[The statement follows:]
Prepared Statement of Don Schneider
Thank you, Chairman Harkin, for holding this important hearing
today on Parkinson's research. As a fellow Iowan, I am especially
honored to be here today to speak to you about Parkinson's disease--
both the incredible toll it takes on its victims and their families--
and the great urgency of providing the federal resources necessary to
cure this dreadful disease.
Fifteen years after my diagnosis, Parkinson's is continuing to
slowly but surely chip away at my quality of life. It has forced me to
leave a job that I loved, placed a heavy burden on my family and at
times each day renders me unable to walk, read a book or even dress
myself. For someone raised as an independent farm boy, I cannot express
the frustration that accompanies this disability.
Let me begin by giving you a little background about myself. I was
born in Clinton, Iowa and raised on a farm in Mt. Carroll, Illinois.
After graduating from high school, I attended radio school at Brown
Institute in Minneapolis, Minnesota. At age 19, I went to work as a
night announcer for KROS radio in Clinton. After serving in a number of
capacities at the station--everything from Announcer to Program
Director--I purchased stock in the company and was named General
Manager in 1987. Professionally, I was active in the Iowa Broadcasters
Association and served as President of the Iowa Radio Network. I was
also very active in the local community--a member of the Kiwanis Club,
helping the United Way's Board of Directors for the Clinton Substance
Abuse Council and was involved in countless fundraisers for various
worthwhile projects in the Clinton area. In addition, I have always
enjoyed working with young people. I was inducted into the Junior
Achievement Hall of Fame for serving as an Applied Economics Advisor. I
have always had a deep love of sports, especially basketball. I tried
to share that with youngsters by coaching junior football and
basketball. Later, I even took up the stripes as a high school
basketball official.
It was in 1988, during a basketball game I was refereeing, I held
out two fingers to indicate two shots when I noticed shaking in my left
hand. My family had begun to notice a blank stare on my face and I
began experiencing slowness of movement and pain in my neck. One visit
to the clinic and I was diagnosed with Parkinson's at the age of 35.
For five years after my diagnosis, I hid it from all but my family.
When people asked, I simply said, ``I have a neurological condition''.
I could relate very well to the feelings expressed by Michael J. Fox
when he was first diagnosed with Parkinson's. You don't want to believe
this is happening to you and you certainly don't want anyone else to
know what is happening to you. What would they think? How would they
treat me? It was extremely difficult after being someone that was
always in charge to be forced to depend on others to help me.
At first, with the help of my medications, I was able to continue
living a relatively normal life. As long as the medicine was working, I
could do just about anything. But eventually, progression of the
disease and side effects of the medications left me no longer able to
count on being fully functional at work. My condition became so
unpredictable that I was forced to end my broadcasting career in 1999.
Today I reside in rural Clinton with my wife, Rita, and three
youngest children, Joseph 17, Sam 14 and Anne 10. My two oldest
children are now finished with school and living on their own. Katie,
21, is serving our country in the U.S. Army. She is stationed in Ft.
Polk, Louisiana where she currently works with a mobile medical unit.
Sarah, our oldest, recently graduated from the University of Iowa and
is now at University Hospitals and Clinics working as a registered
nurse in the Neurology Department--something that certainly takes on
added significance given my condition. I am very lucky to have a
strong, supportive family that has stood by me from the beginning.
That's not to say it has been easy. I can still recall the profound
sadness in the eyes of my family members and the uncertainty and sense
of dread we all felt when word came of my diagnosis. I cannot deny that
each day I worry about what our future will be like. On the one hand,
great progress has been made and many new medications have become
available in just the short time I have been affected. On the other
hand, there is still no known cause and the possibility of being
trapped with an alert, active mind in a body I cannot control is more
frightening than I can describe.
Since giving up my job, we have had to rely on my wife's income
from her job at an accounting firm and Social Security to get by.
Fortunately, she makes a good living, but there is no question that
Parkinson's has taken an economic toll on our family. We are facing the
prospect of soon losing our health insurance with prescription
coverage. With a cost of over $700 a month for my prescription
medication, we will certainly have to make do with a lot less. I often
think about all that my family is missing because of Parkinson's
Disease.
I have tried to channel some of my anger over being diagnosed with
Parkinson's into something positive. I started a Parkinson's support
group in Clinton several years ago, which I still facilitate. This
group of over thirty families has been a great help to me in facing the
daily struggle of life with Parkinson's.
No one knows why or how I got this terrible disease. Is it genetic?
Two of my great uncles had Parkinson's--but one was on my maternal side
and the other was on my paternal side. Does the environment play a
role? I grew up drinking farm water, but so did the rest of my family
and no one else has Parkinson's. The bottom line is we just don't know
what causes Parkinson's. But, I am hopeful that we will have answers
soon. Scientists have made remarkable progress and with adequate
funding could find new treatments and even a cure in my lifetime.
I am not a quitter and I refuse to give up hope. I have always had
a love of old cars, and have used as a motto a line from an old car
movie ``The Gumball Rally''. In that movie as the race is about to
start, a driver in a Ferrari turns to his co-pilot, tears off the rear
view mirror, and says, ``now the first rule of Italian driving--what's
behind me does not matter''. I try to do the same. Keep looking ahead
rather than worry about what I've lost and remember all I have to be
thankful for--most importantly my wonderful family. I hope that by
staying involved and active in the fight for a Parkinson's cure, I can
make a difference in my destiny and that of the million other Americans
suffering from this dreadful disease.
Again, I thank you for the opportunity to be here today.
Senator Harkin. Don, thank you again so much, again for
putting a real human face on what this means to families.
Now, as the most recognizable man on the planet, Muhammad
Ali--we have already said a lot about him--certainly needs no
introduction. He is simply the greatest of all time.
Lonnie Ali has been married to Muhammad for 14 years and
has coordinated all his affairs for the past decade. Among her
many activities related to Parkinson's disease, Mrs. Ali serves
on the board of the Michael J. Fox Foundation for Parkinson's
Research. We welcome you both here, and Mrs. Ali, again, your
statement will be made a part of the record and Muhammad's will
be made a part of the record. Please proceed as you so desire.
STATEMENT OF MUHAMMAD ALI, FORMER HEAVYWEIGHT BOXING
CHAMPION
ACCOMPANIED BY LONNIE ALI
Ms. Ali. Thank you, Chairman Harkin. A little correction. I
have been married to Muhammad 16 years.
I have to count every year.
But thank you and the members of the subcommittee for
inviting Muhammad and me here today for this important hearing
on Parkinson's disease research funding. We are grateful for
your past support and for focusing attention on this important
topic.
We were compelled to be here today because of the troubling
situation we see occurring with regard to Parkinson's research,
that may be unnecessarily delaying progress toward better
treatments and even a cure for Parkinson's. We are here because
Muhammad has never been one to sit back quietly and wait for
things to happen. He is and always has been a fighter, not just
in the ring, but with each and every cause he believes in. We
are here today as champions of the National Institutes of
Health research, who will not stop until we reach the gold, a
cure for Parkinson's.
To the world, my husband is known as an Olympic Gold Medal
winner, the Heavyweight Champion of the World, and a man who
has always stood up for what he believes in. No matter what the
cause, Muhammad has always used his charm and grace and wit to
better the world. From the antiwar movement, to the fight for
civil rights, to his efforts to raise awareness about the
plight of many third world countries, Muhammad has never been
far from the center ring.
Today, however, he is facing an opponent unlike any he has
ever fought. Just as the million other Americans who suffer
from Parkinson's, Muhammad is battling a relentless,
remorseless, insidious thief. Parkinson's recognizes no titles,
respects no achievements, nor bows to any amount of talent,
courage, or character. Parkinson's does not discriminate. There
is no question that Parkinson's is the fight of Muhammad's
life.
But Parkinson's affects more than just those who have the
disease. As the wife, friend, and confidant of someone who
lives with someone with Parkinson's, I can tell you that our
entire family and our close friends have been profoundly
impacted as well. At this time in our lives, we had expected to
be enjoying retirement, continuing to fight for important
causes, and most importantly, enjoying time together as a
family. Parkinson's never stops trying to rob us of those
dreams. Even though Muhammad keeps punching back and refuses to
go down for the count, we are certainly not living the life we
had envisioned.
We often talk about how much more Muhammad would be doing
to make the world a better place, to stand up for those who
cannot stand up for themselves, to fight racism, and to spread
his message of peace. There can be no doubt that Parkinson's is
depriving not only our family, but the Nation and even the
world of Muhammad's full contribution.
But Muhammad is only one man. There are 1 million Americans
suffering from Parkinson's. Imagine what those million
Americans could be doing to better the world if not for this
disease.
While Muhammad and I keep up the fight on a personal level,
scientists are fighting each and every day in laboratories
across the country to find a cure. They tell us that
Parkinson's is the most curable neurological disease. In fact,
at a hearing before this subcommittee on September 28, 1999,
Dr. J. William Langston, president of the Parkinson's Institute
and a member of the scientific advisory board for the Michael
J. Fox for Parkinson's Research, said: ``While science is full
of serendipity and unexpected surprises in research, sometimes
you hit a point where it's time to focus. I truly believe that
we are now at a point where there is enough knowledge that it
is a time to focus. With a focused effort, the pieces are in
front of us, the science is there. I think we can make major
progress towards this disease.''
We have reached a crossroads. We know the science is there
but the money is not. I am proud to serve as a member of the
board of the Michael J. Fox Foundation for Parkinson's
Research. The foundation is doing tremendous work to fund
incredibly promising private research. Now it is time for the
Federal Government to get into the fight for real. We must
provide the Federal funds necessary to carry out this promising
research. As the world's leader in biomedical research, our
Government has a responsibility to realize the tremendous
scientific potential and provide adequate funding.
Two-and-a-half years ago, the NIH established the
Parkinson's Disease Research Agenda, which called for a $1
billion increase in Parkinson's funding. Unfortunately, the
Parkinson's agenda is not being fully funded. In fact, there is
a $100 million shortfall for this year alone.
Time is of the essence. People with Parkinson's do not have
any time to waste. This tragic underfunding may lead to missed
opportunities for better treatments and even for a cure.
Congress and the NIH have an opportunity to oversee effective
treatments and possibly a cure for Parkinson's, if the
necessary funding is made available.
Muhammad has never been one to do anything halfway, and he
has never settled for doing something second best in anything
that he has done, in the ring, in his work on humanitarian
causes, or in his personal life. We implore the NIH and
Congress to not go halfway on the Parkinson's Research Agenda.
The Federal Government must aim high and work hard to reach the
goal of finding a Parkinson's cure.
PREPARED STATEMENT
Our challenge to you today is to champion this research and
to fully fund the Parkinson's Disease Research Agenda by
committing $353.3 million for year 3. Together let us knock
Parkinson's disease down for the count.
Thank you very much.
[The statement follows:]
Prepared Statement of Lonnie Ali
Thank you, Chairman Harkin and Members of the Subcommittee for
inviting Muhammad and me to be here today for this important hearing on
Parkinson's Disease research funding. We are grateful for your past
support and for focusing attention on this important topic.
We were compelled to be here today because of the troubling
situation we see occurring with regard to Parkinson's research, that
may be unnecessarily delaying progress toward better treatments and
even a cure for Parkinson's. We are here because Muhammad has never
been one to sit back quietly and wait for things to happen. He is and
always has been a fighter, not just in the ring, but with each and
every cause he believes in. We are here today as champions of National
Institutes of Health (NIH) research, who will not stop until we reach
the gold--a cure for Parkinson's.
To the world, my husband is known as an Olympic gold-medal winner,
the Heavyweight Champion of the World and a man who has always stood up
for what he believes in. No matter what the cause, Muhammad has used
his charm, grace and wit to better the world. From the antiwar
movement, to the fight for Civil Rights to his efforts to raise
awareness about the plight of many Third World countries, Muhammad has
never been far from the center ring.
Today, however, he is facing an opponent unlike any he has ever
fought. Just as the million other Americans who suffer from
Parkinson's, Muhammad is battling a relentless, remorseless, insidious
thief. Parkinson's recognizes no titles, respects no achievements, nor
bows to any amount of talent, courage or character. Parkinson's does
not discriminate. There is no question that Parkinson's is the fight of
Muhammad's life.
But Parkinson's affects more than just those who have the disease.
As the wife, friend and confidant of someone with Parkinson's, I can
tell you that our entire family, and our close friends, have been
profoundly impacted as well. At this time in our lives, we had expected
to be enjoying retirement, continuing to fight for important causes
and, most importantly, enjoying time together as a family. Parkinson's
never stops trying to rob us of those dreams. Even though Muhammad
keeps punching back, and refuses to go down for the count, we are
certainly not living the life we had envisioned.
We often talk about how much more Muhammad would like to be doing
to make the world a better place--to stand up for those who can't stand
up for themselves, to fight racism and to spread his message of peace.
There can be no doubt that Parkinson's is depriving not only our
family, but the nation, and even the world, of Muhammad's full
contribution. But Muhammad is only one man. There are one million
Americans suffering from Parkinson's. Imagine what those million
Americans could be doing to better the world if not for this disease.
While Muhammad and I keep up the fight on a personal level,
scientists are fighting each and every day in laboratories across the
country to find a cure. They tell us that Parkinson's is the most
curable neurological disease. In fact, at a hearing before this
Subcommittee on September 28,1999, Dr. J. William Langston, President
of the Parkinson's Institute and a member of the scientific advisory
board for The Michael J. Fox Foundation for Parkinson's Research, said:
``[W]hile science is full of serendipity and unexpected surprises in
research, sometimes you hit a point where it's time to focus. I truly
believe that we are now at a point where there is enough knowledge . .
. that it's time to focus. With a focused effort, the pieces are in
front of us, the science is there. I think we can make major progress
towards this disease.''
We have reached a crossroads. We know the science is there--but the
money is not. I am proud to serve as a member of the board on The
Michael J. Fox Foundation for Parkinson's Research. The Foundation is
doing tremendous work to fund incredibly promising private research.
Now it's time for the federal government to get in the fight for real.
We must provide the federal funds necessary to carry out this promising
research. As the world's leader in biomedical research, our government
has a responsibility to realize the tremendous scientific potential and
provide adequate funding.
Two and a half years ago, the NIH established the Parkinson's
Disease Research Agenda, which called for a $1 billion increase in
Parkinson's research funding over five years. Unfortunately, the
Parkinson's Agenda is not being fully funded. In fact, there is a $100
million shortfall for this year alone.
Time is of the essence. People with Parkinson's don't have any time
to waste. This tragic underfunding may lead to missed opportunities for
better treatments and even a cure. Congress and the NIH have an
opportunity to oversee effective treatments and possibly a cure for
Parkinson's, if the necessary funding is made available.
Muhammad has never done anything halfway, and has never settled for
second best in anything he has done--in the ring, in his work on
humanitarian causes or in his personal life. We implore the NIH and
Congress to not go halfway on the Parkinson's Research Agenda. The
federal government must aim high and work hard to reach the goal of
finding a Parkinson's cure.
Our challenge to you today is to champion this research and fully
fund the Parkinson's Disease Research Agenda by committing $353.3
million for year three. Together, let's knock Parkinson's Disease down
for the count.
Thank you very much.
Senator Harkin. Now the founder of the Michael J. Fox
Foundation for Parkinson's Research, someone who has given us
so much hope and encouragement and courage through his book and
through his forming this foundation. This is Michael J. Fox's
third appearance before this subcommittee. Mr. Fox, we welcome
you back.
STATEMENT OF MICHAEL J. FOX, FOUNDER, THE MICHAEL J.
FOX FOUNDATION FOR PARKINSON'S RESEARCH
Mr. Fox. Thank you and good morning. Mr. Chairman, Senator
Specter, and members of the subcommittee, thank you for this
opportunity to testify.
Is it just me or were you sitting in different seats the
last time I was here?
Senator Harkin. I am constrained to say it is ``back to the
future.''
Mr. Fox. I apologize if that is a sore subject for some
members of the subcommittee, but I bring it up only to make the
point that it is a tribute to each of you that irrespective of
the musical chairs of electoral politics and who sits in which
seats on the dais, the subcommittee's commitment to biomedical
research funding has remained consistent and committed. And we
are very grateful.
Mr. Chairman, all Iowans and all Americans can be grateful
and proud of your leadership on issues of health, including
your continuing efforts to make biomedical research a higher
national priority. You and Senator Specter have spearheaded the
historic effort that will soon succeed in doubling the budget
for the National Institutes of Health over 5 years. The fact
that you have done so, despite difficult budgetary time,
changing administrations, and changes in majority control,
underscores the notion that illness and injury truly are non-
partisan issues that need bipartisan solutions.
I am grateful for the subcommittee's invitation but I would
not have come back again if I did not feel I had something
constructive to add. Although we appreciate this forum, none of
us here today has any interest in becoming another of this
city's self-perpetuating cottage industries.
Back in 1999, I testified that Parkinson's research was far
ahead of the money, that high quality and high impact projects
are being slowed down or stalled completely by the lack of
available support. In addition to appealing to you and to the
NIH, it was clear that there was more that we could do
ourselves. It did not take long to find a group of like-minded
people and together we launched a foundation with the single
purpose of stimulating and supporting research, strategic
thinking, and collaborations to accelerate the cure for
Parkinson's.
We are committed to enabling the work of scientists, and to
do so, we focus on the process of identifying, funding, and
tracking research. We try to target where we can have the
biggest impact and to employ the best methods to shorten the
funding cycle, share the outcomes of research, and stimulate a
coordinated effort to translate promising findings into a cure.
Some of our programs support investigator-initiated grants,
the bread and butter of the NIH system and an indispensable
mechanism for supporting new ideas. But with our emphasis on
higher-risk, higher-reward projects, we have streamlined the
NIH model and applied some of our own innovative thinking.
We have also enlisted scientists to identify the highest
priority areas of research and recommend proactive steps we can
take to move the field forward in meaningful ways. Such
assessments have led to several specific funding initiatives,
including a search for a conclusive diagnostic test or
biomarker for Parkinson's, and development of a cell line
specifically for the study and treatment of Parkinson's.
Last fall we launched a $2.2 million initiative to develop
cell lines with characteristics deemed relevant to Parkinson's.
As with our other programs, the scientific response was
overwhelming. We received applications from a veritable who's
who of cellular biologists worldwide. The number and the
quality of the proposals compelled us to double the program's
budget to $4.4 million, which made it possible for us to
support a portfolio of projects exploring all the promising
techniques for creating cell lines from adult, fetal, and
embryonic cells. The number and diversity of these programs
will allow for a meaningful comparison of these exciting
technologies.
In our request for applications, we made it clear that we
valued results over technique or cell source. Our program is to
develop an effective tool to study and treat Parkinson's, not
to support new technologies for their own sake or to pick
favorites among emerging therapies. As any patient will tell
you, their favorite therapy is the one that works. This is an
obvious and logical approach if your goal is to cure a disease,
but often the political debate can lead to arbitrary decisions
or otherwise obscure the fact that the goal of the research is
to treat, heal, and cure.
I want to commend you, Senators Harkin and Specter, along
with Senators Feinstein, Hatch, and all your other bipartisan
colleagues, for supporting the Human Cloning Prohibition Act of
2002, which strikes the necessary balance between development
of potentially lifesaving research and inappropriate
applications of this powerful technology. It is important to
make clear that the debate is not about promoting one type of
research over others. It is about protecting researchers from
being demonized or criminalized so they can go about their work
exploring new opportunities to treat illness and disease.
Development of such promising new therapies puts us on the
threshold of a new era of medicine. Today a neurologist may be
able to do little more than tell you the name of the disease
that is taking away your life, or in some cases he or she may
be able to give you a prescription or two to ease the symptoms
for a few years. It is not a great proposition, but there is a
paradigm shift underway. Understanding of the brain and of
neurological disorders is advancing at a staggering pace,
moving from definition of the disease, to treatment, to the
possibility of repairing the brain and restoring lost function.
The time has come when the brain is no longer just a place for
research, it is a place for cures.
The NIH recognizes this shift and has taken some steps to
respond. Unfortunately, vacant leadership positions have
prevented the bold action we need. Our foundation has succeeded
thus far mostly by tapping into the enormous backlog of
promising, yet underfunded and unfunded science. We did not
create this opportunity. We are simply responding to it with
whatever resources we can muster. As exciting and gratifying as
it is, seeing the possibility only increases our impatience and
sense of frustration of what is not getting done. NIH has the
resources and the infrastructure to do much more.
To meet the opportunity, I encourage the new NIH Director
to immediately fill the open NINDS Director position and to do
so with someone committed to using all available tools,
including the Director's discretionary budget authority. I
believe the NIH should responsibly pursue all available
regenerative therapies for Parkinson's and other diseases and
adopt an aggressive, proactive Bunsen burner to bedside
approach to creating cures not just research.
I will shorten my comments.
prepared statement
In describing our efforts, we often make analogies to great
achievements like the moon shot. But I am here to tell you that
administering a successful research program is not rocket
science. It is mostly common sense and the will to get things
done. And we are going to get this done. This subcommittee,
this Congress, and the NIH have the opportunity to make it
happen in time for many more people today living with
Parkinson's.
Thank you.
[The statement follows:]
Prepared Statement of Michael J. Fox
Mr. Chairman, Senator Specter, and members of the Subcommittee,
thank you for this opportunity to testify.
Is it just me, or were you sitting in different seats the last time
I was here?
I apologize if that is a sore subject for some members of the
Subcommittee, but I bring it up only to make the point that it is a
tribute to you that irrespective of the musical chairs of electoral
politics, and who sits in which seats on the dais, this Subcommittee's
commitment to biomedical research funding remains constant.
Mr. Chairman, all Iowans, and indeed all Americans, should be
grateful for your leadership on issues of health, including your
continuing efforts to make biomedical research a higher nation
priority. This Subcommittee--along with other individuals in this
room--have spearheaded a historic effort that will soon succeed in
doubling the budget for the National Institutes of Health over five
years. You have accomplished this feat through difficult budget times,
through changing administrations, and even through changes in majority
control--an achievement that underscores the notion that illness and
injury truly are non-partisan issues needing bipartisan solutions.
I am grateful for the Subcommittee's invitation, but I would not
have come back again if I did not feel I have something constructive to
add. None of us here has any interest in becoming another of this
city's self-perpetuating cottage industries. Our appeals to you are
part of our larger effort to accelerate the cure for Parkinson's
disease. Much progress is being made, but there is no question that a
well-funded and coordinated effort by the federal government would
hasten the pace. And as you have already heard, time lost to
Parkinson's inevitably means that lives are lost as well.
You've also heard from Dr. Isacson about the wide array of
promising research opportunities relating to Parkinson's. He and dozens
of other senior investigators make clear the inevitability of a
breakthrough. Taken together, their message is unmistakable: curing
Parkinson's is not a question of ``if''? It is a question of ``when''?
Back in 1999, I testified that Parkinson's research was far ahead
of the money. Joan, Dr. Bill Langston, and I all testified that high
quality and high-impact projects were being slowed down or stalled
completely by the lack of available support. In addition to appealing
to you and the NIH, we saw there was more we could do ourselves. With
their help and advice, and together with a group of like-minded people,
we launched a foundation with the single purpose of stimulating and
supporting research, strategic thinking, and collaborations to
accelerate the cure for Parkinson's.
We are lay people committed to enabling the work of scientists, and
to do so we focus on the process of identifying, funding, and tracking
research. We try to target where we can have the biggest impact and to
employ the best methods to shorten the funding cycle, share the
outcomes of research, and stimulate a coordinated effort toward the
cure.
Some of our programs support investigator-initiated grants--the
bread and butter of the NIH system and an indispensable mechanism for
supporting new ideas--but in keeping with the higher-risk, higher-
reward nature of our mission we've streamlined the NIH model and added
our own wrinkles.
We've also enlisted scientists to identify the highest-priority
areas of research and recommend proactive steps we can take to move the
field forward in meaningful ways. Such assessments have lead to several
specific funding initiatives, including the development of a cell line
specifically for the study and treatment of Parkinson's.
One month after the meeting that made the recommendation we
launched a $2.2 million initiative to develop cell lines with
characteristics deemed relevant to Parkinson's. We received
applications from a veritable who's who of cellular biologists
worldwide. The number and quality of the proposals compelled us to
double the program's budget to $4.4 million, which allowed us to
support a portfolio of projects exploring all the promising techniques
for creating cell lines from adult, fetal and embryonic cells. The
number and diversity of these programs will allow for a meaningful
comparison of these exciting technologies.
In our request for applications we made it clear that we valued
results over technique or cell source. Our program is to develop an
effective tool to study and treat Parkinson's, not to support new
technologies for their own sake or to pick favorites among emerging
therapies--any patient will tell you that their favorite therapy is the
one that works. This is an obvious and logical approach if your goal is
to cure a disease, but often the political debate can lead to arbitrary
decisions or otherwise obscure the fact that the goal of the research
is to treat, heal, and cure.
I want to commend you Senators Harkin and Specter, along with
Senators Feinstein, Hatch and all your other bipartisan colleagues for
supporting the ``Human Cloning Prohibition Act of 2002,'' which strikes
the necessary balance between development of potentially life-saving
research and inappropriate applications of this powerful technology. It
is important to make clear that the debate is not about promoting one
type of research over others, it is about protecting researchers from
being demonized or criminalized so they can go about their work
exploring new opportunities to treat illness and disease.
Development of such promising new therapies puts us on the
threshold of a new era of medicine. Today a good neurologist may be
able to do little more than tell you the name of the disease that's
taking away your life, or in some cases he or she may be able to give
you a prescription or two to ease the symptoms for a few years. It's
not a great proposition, but there is a paradigm shift underway.
Understanding of the brain and of neurological disorders has advancing
at a rapid pace, moving from definition of the disease to treatment to
the possibility of repairing the brain and restore lost function.
Not too long ago it was an anathema to think that the brain has any
capacity to regenerate and repair itself. But in recent year many
scientists have embraced this recently revolutionary concept and run
with it. Dr. Isacson, for example, is so convinced in the potential of
the science that he has named his lab the ``Neuroregeneration
Laboratory.''
NIH recognizes this shift and has taken some appropriate steps to
respond. Nonetheless, they still trail behind the scientists out on the
cutting edge--those whose experience increases our confidence that a
cure is within reach. Our own experience shows the type of efficient
funding process that is possible and the level of interest there is in
doing the necessary work. All of this is tremendous progress, but it
also increases impatience and sense of frustration over what is NOT
getting done.
To meet the opportunity, I encourage the new NIH Director to fill
open NINDS Director position, and to do so with someone committed to
using all available tools--including the Director's discretionary
budget authority--in the fiscal year 2002 and fiscal year 2003 budgets
to direct significantly more funding toward implementation of PD
Research Agenda. I believe the NIH should responsibly pursue all
available regenerative therapies for Parkinson's and other diseases,
and to adopt and an aggressive, proactive ``Bunsen burner to bedside''
approach to pursuing cures, not just research.
I want the Subcommittee to know that we in the private sector hope
to engage in greater collaboration with NIH when tapping Parkinson's
researchers for advisory and planning meetings. The goal is to reduce
the number and replication of meetings and allow more time for the best
scientists to work in their labs.
When I first appeared before this Subcommittee I spoke about my
experience with Parkinson's disease. I did so in very personal terms
because that is what I know. I know my own Parkinson's, which is
different than Muhammad's, or Joan's, or Don's, or Milly Kondracke's.
Every person who is diagnosed with Parkinson's is given their own
custom version of the disease--and no operating instructions, I might
add.
The other thing given to every person diagnosed--particularly the
growing number of young-onset cases--is a reason to hope.
We are told that scientists are making great progress and that with
the proper funding there may be a cure in five or ten years. We hear
that there is no shortage of good ideas, just a shortage of research
money. More recently we have been told that more money is on the way.
The heroic efforts of the grassroots advocacy community are having an
impact and Congress is taking steps to ensure more Parkinson's research
funding. Congress passed Parkinson's-specific legislation, asked NIH to
develop a Parkinson's Research Agenda, and last year adopted strong
report language urging more funding and full implementation of the
research agenda.
These have each been significant accomplishments, and we are all
grateful to this Subcommittee and your colleagues in the Senate and
House for your support. And yet despite these legislative achievements,
support of Parkinson's research has failed to keep pace with the
overall growth in NIH's budget, it has not meet the goals of the NIH
Research Agenda and it falls far short of the scientific opportunity.
Is it that this system is not designed to systematically and
aggressively study, treat, and cure a disease? If that's true, we have
got to reinvent the system.
NIH has a vital roll funding basic research and supporting
scientific explorations. But when there are opportunities to reduce
human suffering and societal costs by curing a disease like
Parkinson's, then I think it is appropriate for the National Institutes
of Health to commit a fraction of it's resources to actually treating
the nation's health. Parkinson's disease is both an individual and
national challenge. We ought to act as surely as we act in response to
other challenges to our health, our lives, and our society.
I would not take this coveted time before the Subcommittee to argue
for something than cannot be done. Our experience is evidence that it
can. And we'll keep at it, because unlike some other reports you may
have heard, we have yet to determine any shortage of interest in
Parkinson's research or in high-quality, high-impact projects that
await funding. Don't let anyone tell you that everything that can be
done is being done or that the scientific community has reached its
capacity for Parkinson's research.
What's more, I believe we are at the ``tipping point'', the moment
of critical mass when the momentum towards the cure becomes
irresistible and the only remaining question is whether the federal
government will be helping lead the process, or will it be trailing
along behind?
In describing our efforts we often make analogies to great
achievements like the moon shot. But I am here to tell you that
administering a successful research program is not rocket science. It
is mostly common sense and the will to get things done. And we're going
to get this done. This Subcommittee, the Congress, and the NIH have the
opportunity to make it happen in time for many more people living today
with Parkinson's.
Thank you.
Senator Harkin. Michael, that was a very profound
statement. Thank you so much.
Before I turn to Senator Specter, who would like to ask
some questions and make a statement, we have now been joined
also by another former U.S. Senator and former Secretary of
Transportation in the administration of President Carter. Our
former colleague, Senator Brock Adams of the State of
Washington, is also here.
Senator Specter.
Senator Specter. Thank you very much, Mr. Chairman, for
deferring to me. I am going to have to excuse myself in a few
moments and wanted a chance to make a few closing comments.
This is an unusual hearing where there is applause.
Customarily there is tough cross examination on witnesses when
we have to get into some of the very difficult matters. But
there is a lot of love in this room and a lot of unity of
purpose to try to reach a common goal, and that ought to be
noted.
This subcommittee will pursue these issues with great
intensity, as we have, and we will try to see to it that there
is full funding for Parkinson's, because it is true that the
money is there. The funding is there and it is a matter of
allocation. We try to depoliticize the matter by leaving it to
the discretion to the National Institutes of Health, but we
have a view and they do listen to us more than occasionally.
Dr. Ruth Kirschstein is smiling. She had been acting
Director of NIH and she is now Deputy Director. I join Senator
Harkin in saluting you, Dr. Kirschstein, for your great service
and the award which you have received today.
I compliment you, Mr. Fox, on many things, but you noticed
the role reversal up here. Senator Harkin has the gavel. I
touch it. It is almost too hot to handle.
Senator Harkin had been the chairman back in 1994 and I
took over in 1995 for 6\1/2\ years. But we have had a seamless
transition. It does not make any difference between Tom Harkin
and Arlen Specter who the chairman is. I think we both learned
a long time ago, if you want to get something done in
Washington, you have to cross party lines. I know the American
people are sick and tired of the bickering that occurs in
Washington, which is all too frequent, but not on this
subcommittee and not on this purpose. And we are determined to
move ahead.
Joan Samuelson, I know exactly what you mean with your
comment about no time to lose. I think that is exactly right.
You only have your health once, and there is no time to lose. A
constituent of mine, Jim Cordy, in Pittsburgh, who suffers from
Parkinson's carries around an hourglass, and whenever he sees
me, he inverts it to let me know that the sands of time and the
seconds of his life are ticking away. That is the kind of
intensity which we appreciate and understand.
Mr. Don Schneider, you have still got a strong voice. You
can tell radio there. You can tell projection. We hear you. We
hear you loud and clear.
And thank you, Dr. Penn and Dr. Isacson, for what you have
contributed here today.
Muhammad Ali was in Pittsburgh not too long ago. He has
great resiliency in responding to the bell to come out
swinging, and with The Champ in our corner and with Mrs. Lonnie
Ali's eloquent statement, we have our work cut out for us.
We have special momentum from Claiborne Pell, Mac Mathias,
Brock Adams, and Mrs. Russell Long, and really from millions
and millions of Americans.
I would conclude on the note which Michael J. Fox sounded
about the pending legislation. Everyone in America is either
afflicted with the disease, has a family member afflicted with
the disease or knows somebody who is. If there is an
understanding that this legislation could cripple the efforts
to use stem cells to cure Parkinson's, Alzheimer's, heart
disease, and cancer, et cetera, America would rise up in an
avalanche. That is a message we are working to carry forward.
This hearing is very, very helpful because of the focus of
attention it has brought on this critical problem.
So, I thank you and I give you the pledge of the
subcommittee--I know I speak for Tom Harkin and all the
members--that we will continue fighting, and I think we are
going to win it. Thank you all very much.
Senator Harkin. And though not a member of the committee,
but again, one of the most effective and powerful voices in
fighting Parkinson's in the entire United States Congress,
Senator Paul Wellstone.
Senator Wellstone. Thank you, Tom.
You know, Arlen, I do not know that we always agree, but I
cannot think of a word that you just uttered that I could
disagree with. And I just would like to say to everybody here,
those who testified, those who came, everyone, and all the
people that your represent around the country, it is an
absolute honor to work with you. We will all take this journey
together, and there is no doubt in my mind that we will
succeed. Thank you.
Senator Harkin. Thank you very much, Paul.
Well, since they just both gave my speeches, I will just
refrain from giving a speech here. But I would like to ask a
couple of questions, make a point, and then maybe ask a couple
of questions.
Dr. Penn, I know that you put that chart up that pointed
out the increases in Parkinson's disease funding in the mid-
1960's that was above the annual increases at NIH.
Dr. Penn. Sir, it is 1996 to 2001.
Senator Harkin. 1996, 1997, 1998, 1999, and 2000.
Dr. Penn. Right, over 5 years.
Senator Harkin. For argumentative purposes and debate
purposes, we can all use percentages to try to make our case.
When people tell me that we have had this huge percentage
increase in anything, I always ask one question. What is the
baseline? You see, to go from 0 to 1 is an infinite percentage
increase. So, I have got to know what the baseline is. Quite
frankly, yes, I would agree that percentages were higher, but
we started from a very, very low baseline.
So, I think what we have to look at in cases like this,
especially in biomedical and medical research, is where are you
in the spectrum from knowing nothing to translating it into a
cure. Where are you on that?
It would seem to me that in this specific case of
Parkinson's, that needle is way past the halfway mark in terms
of knowing nothing, starting the basic research, to getting to
the point of doing translational types of applications. Now,
that is the point at which we have to focus not so much on
percentages and percentage increases, but what are the requests
out there for projects, what are we capable of doing in
translating this research to the bedside, what are we capable
of doing right now in moving ahead from the basic research,
which we have passed a lot by--Dr. Isacson spoke about it--to
really translating this into clinical trials?
So, I am not interested in the percentage. I want to know
how much money overall will it take to move that needle towards
the cure from where we are right now. And that is what we are
focused on here. What is it going to take dollar-wise, not
percentage-wise?
Now, I know the President's budget has $215.1 million for
Parkinson's funding for next year. That is up from $198.8
million from last year. That percent would be 8.2 percent. But
again, I would like to get off the percent increase. I want to
know what is it going to take dollar-wise. I do not know if you
could speak to that or not, Dr. Penn.
Dr. Penn. I couldn't possibly estimate dollar-wise. What I
can say is that at NINDS, and with the rest of the institutes,
we are convinced that the scientific advances have been really
excellent, that all the investigators that came and
participated and were involved in the Parkinson's Research
Agenda that have put in applications that went successfully
through rigorous peer review have been funded. We funded 80
applications in 2 years between 2000 and 2002 on----
Senator Harkin. 80 percent?
Dr. Penn. 80 brand new applications. The average cost of
these at this point is about $400,000. We have got the
initiatives out there. We are funding the Udall centers. And
when we had the meeting of the consortium in January of 2002 to
look again at this agenda and where we were going, the
investigators did not want to talk budget. They wanted to talk
science, and they were very pleased at the fact that all the
areas of the agenda were really moving forward. So, as I tried
to say in my opening statement, I think we are on the verge of
excellent control and a much better quality of life, though we
are going to need to work on all of the things that Dr. Isacson
mentioned to achieve a cure.
Senator Harkin. Well, the Parkinson's Research Agenda is
intended to answer the dollar question. I might turn to Joan on
this and just ask you. The Parkinson's Research Agenda is
asking for, as Mrs. Ali mentioned, $353.3 million. Again, I do
not need you to go into great detail, but how do you arrive at
a figure like that?
Ms. Samuelson. Well, the scientists did it. They met and
discussed several areas of research with great promise in
detail. They had the experts from all the areas. And they put
dollar amounts on it. It is interesting, because we had a
research plan just sponsored by the Parkinson's Action Network
before the NIH's, and it arrived at similar numbers. It was a
matter of the scientists who are the best in the field, who
understand what it takes to run the lab and to do the work and
have the wish list of projects that they are not funding,
devoting their time to figuring it out. That is the same thing
that happened with the NIH's. It was a very deliberate,
elaborate process with a room full of investigators who are NIH
recipients and understand the process. It was a very sober,
careful process that arrived at these numbers that would
gradually add up to an increase of $1 billion over 5 years.
Senator Harkin. So, from that, you are saying that there is
enough in the scientific community to warrant that kind of
spending that would be solid, good research, and I assume some
trials within that.
Ms. Samuelson. Absolutely.
Senator Harkin. Dr. Penn, will we be doing some trials in
the next year?
Dr. Penn. Yes, we will and we have the agents. The meeting
was yesterday on the neuroprotective agents that are
potentially useful. Of course, they have to be studied in pilot
trials before you put them safely into phase III trials on
humans.
We also are doing this trial with the Veterans
Administration on the deep brain stimulation which I think will
really improve control enormously. It also has the potential of
improving the motor side effects of L-dopa, and that would be
tremendous because L-dopa is a wonderful drug. It just causes
all kinds of side effects.
We have got to replace the cells, though. I will not deny
that.
Senator Harkin. Well, that leads us to Dr. Isacson then.
Two things I want to ask you about. I understand that your
center is investigating a number of different neurological
disorders, Alzheimer's, Huntington's, ALS, Parkinson's. There
may be others that I do not know about. Which of those do you
believe is closest to actually having some form of a cure?
Dr. Isacson. Oh, I think it is absolutely Parkinson's
disease. The understanding of the underlying disease process is
clearer in that case and also probably the treatments are going
to be simpler in the sense that once you have the science.
You need, however, to build capacity here in the sense that
the Parkinson's Research Agenda that was mentioned--that is a
scientific document that has been evaluated in terms of what
you would need in terms of funding. But to implement that
requires an effort. It requires innovation also in the way that
the centers are organized. We talk now about core facilities to
build up services for the scientific labs to move faster. There
is a need to build capacity into the system. Even when you have
made a scientific discovery, you need to move it forward.
I feel that the scientists and clinicians involved in this
effort need to work with NIH. We seem to have a good
understanding and agreement on the pieces here, but your
leadership on this issue and pointing out that we need to take
a very aggressive path forward that we understand is a
reasonable thing to do.
Senator Harkin. Dr. Isacson, I understand also that by
moving ahead aggressively in Parkinson's--it is my
understanding at least from your testimony and others'--that
may lead to other avenues of cures for other neurological
disorders.
Dr. Isacson. If I may comment.
Senator Harkin. Yes, please.
Dr. Isacson. I am glad you asked that. I am convinced that
when we talk about treatment modalities, most of us know we can
go to the pharmacy and we get a drug. But there are new
modalities that will come out of what we have discovered and
worked on in the States for a long time, for example, the
genome project. All these knowledge bases in science are likely
to generate new technologies, new modalities. And when we break
open the door to new treatments for Parkinson's disease, there
is going to be a lot of movement also for other diseases, and I
am thinking about ALS, Huntington's disease, even spinal cord
damage. So, I can assure you that the scientific community
again agrees on this, that it is useful and reasonable to
spearhead Parkinson's disease, to open up the new treatment
modalities.
Senator Harkin. I understand that you have had some notable
success--and you mentioned it--in using embryonic stem cells in
rats that were undifferentiated that you put into the brains of
rats. You had instilled in them the Parkinson's-like disease
and these rats have recovered. Is that so?
Dr. Isacson. That is correct.
Senator Harkin. Is it not so that we are about 95 percent
like a rat?
I do not mean we politicians. I am not saying that.
I am saying we as humans, I think genetically. The genes.
Do we not share about 90-some percent? I do not know what it
is, but it is pretty close.
Dr. Isacson. Just to be contradictory, I think that none of
the psychology seems to overlap.
But biologically speaking, you are right.
Senator Harkin. Genetically speaking.
Dr. Isacson. Genetically speaking, there is a huge overlap.
What we learn from animals--we call them animal models--we can
usually create models for new therapies. One can call them
prototypes to have a more general understanding. And those
prototypes that we build, sometimes even in fruit flies, give
us knowledge and insight about molecular mechanisms and what I
call the new therapeutic modalities, new technologies to help
the patients.
So, yes, the kind of work we have done on stem cells is
important. It is very clear that we can obtain the cells that
die in Parkinson's through stem cell work, and as I mentioned
previously, I think it is absolutely necessary to have freedom
of research typical of our country to pursue that vigorously as
you have indicated in your bill, for example, on nuclear
transplantation.
Senator Harkin. Give me some idea. When do you think we
would actually--I mean, looking ahead, if we had a robust
increase in Parkinson's funding for the next year, take me down
the road a little bit. I can ask Dr. Penn this or maybe even
Joan. I will ask anyone. When do you think we might actually
see some human clinical trials?
Dr. Isacson. Well, my opinion, in this case, of course, is
an opinion.
Senator Harkin. That is all I am asking.
Dr. Isacson. My thinking on this is that we are very close.
There are a number of these research areas, defined in this
Parkinson's Research Agenda by NIH, that are likely to generate
clinical trials. As mentioned by Dr. Penn, neuroprotective
trials for up to $500 million over the next 7 years will give
us insight about new drugs that can prevent the cells from
dying. We are looking also at gene therapy, sometimes
misunderstood, but again, taking advantage of the molecular
revolution, genome project, to look at new drugs that use
therapeutic genes. That is likely to move into pilot clinical
trials quite soon, maybe before 5 years.
So, to give you an impression, I think a number of these
efforts are moving along, as you said I think correctly, in the
process towards what is reasonable. I always say that FDA is
sometimes lambasted for not being responsive, but in the end we
come there with our ideas and they look at them if they are
safe, and then we test them. But there is a process there.
Senator Harkin. Dr. Penn, anything else on that?
Dr. Penn. I would say that FDA is actually a partner. We
have talked to them about how we would move when using the
approved ES cell lines in people because, after all, there are
several issues there. So, they are waiting in the wings for us
to get to that point.
I have talked to our own major investigator in this area
who is in our intramural program who is proceeding to, as I
said in the statement, drive the human ES cells toward dopamine
cells. He thinks that will take him 1 to 2 years to just do it,
and then, of course, you have to get it into the brain safely
and you have to fulfill the FDA guidelines. And then we could
actually get to a pilot clinical trial in people.
But again, science moves up and then it moves back, and you
cannot always predict. So, I do not want to give you an exact
date. But we fully intend to move into clinical trials with the
approved cell lines as soon as we can.
Senator Harkin. That brings me to Michael Fox then. What
you have been doing with your foundation on the fast track
funding process that your foundation has worked out with NINDS,
can you tell us just again, Michael, how this works and what
you have been able to do so far?
Mr. Fox. To sum it up, basically we approach this problem--
and one of the reasons why I went through the things that we
had done was not so much to blow our horn, but to show that
what this really calls for I think--our proximity to the goal
calls for really an innovative approach and to know that if we
had--just, for example, the amount of time that it takes for an
application for a grant, if we can trim those processes in a
responsible way, if we can make it easier for the scientists to
do what they need to do and just take an innovative approach to
the way the machinery of science normally works, we can hasten
our march toward a cure.
So, what we were able to do was to cut down. We put out an
RFA, request for application, for our first round of grants. I
believe that the time frame was something like 3 months, much
shorter. What happens then is you attract a lot of different
researchers that might not have been able to do it otherwise
and you widen the field of people who want to get involved and
then you widen the talent pool.
What had happened in our case was we were very fortunate to
have the NIH come to us and comment on that fast track and join
us and help us fund some of those proposals. So, it was a very
exciting response from them and very responsible, and we were
thrilled. For us, it really showed that there can be innovative
partnerships and goal-oriented partnerships that make it easier
for scientists to do the work.
There is nothing harder for a scientist than to initiate a
field of study and then have funding dropped out or to not know
what they are getting into. It is not a question sometimes of a
scientist not wanting to do the work or not having work to do,
but he is a person too and he or she has responsibilities to
their employees and to the lab and to their families. So, they
need to know that they will be backed all the way and that
things will be made to facilitate their work. These are not
wizards in the sky. These are people doing real work. So, we
need to appreciate that and make it easier for them.
Senator Harkin. Dr. Penn, how do you feel the partnership
is working?
Dr. Penn. The partnership is working. We were very
fortunate to be able to partner with the Michael J. Fox
Foundation.
And just for the record, the reviews for those innovative
fast track grants actually occurred on September 11, and people
finished the reviews because it was so important and did not
try to--they could not leave town. We could not even get back
to NIH. But it was accomplished. We have a great group.
We have always worked with voluntary organizations to
identify new and promising investigators, and to try to start
up research, because those folks do have to go through peer
review ultimately for their next grants, and we like to make it
as straightforward and as promising for them as possible.
Senator Harkin. Again, congratulations on the foundation
and what you are doing with this partnership is very
innovative. It is something I have not seen before.
Mr. Fox. Thank you. That is what we need, though.
Senator Harkin. We might use the model for other things
too, you know.
Mr. Fox. I did not have a chance to say it early but
everybody on this panel I thank personally for the things that
they have done. I think a lot of people bring innovative
thinking to this problem but the problems are so real and the
need is so real and the urgency is real. And we really feel we
can get this done.
Senator Harkin. Don Schneider, I have a couple of
questions, but one I really have got to ask you. What year is
that red Corvette?
Mr. Schneider. 1977.
Senator Harkin. Is that right? I had a 1977 Corvette. Well,
we cannot take this time to talk about Corvettes.
Mr. Schneider. I can dust it for fingerprints.
Senator Harkin. We will do it later sometime.
As somebody who has been very active all his life and taken
charge and everything, it would be helpful for you to put a
human face on things, just talk a little bit. What did you have
to do to get ready for this morning?
Mr. Schneider. When I get up in the morning, I cannot walk.
My feet shuffle like they are stuck to the floor. I tremor,
shake the whole bed, until my medications kick in. Then once my
medications kick in, it is just like a light switch. I go from
not being able to move to being able to do anything. That lasts
for a couple hours, and then the next dose is due. That is my
day.
Senator Harkin. Mrs. Ali, how about you and how about
Muhammad? How is his day?
Ms. Ali. Yes, Muhammad has been quite fortunate because he
was diagnosed with Parkinson's in 1981, so he has had it for
over 20 years and probably had it before then. But I have seen
the progression in the last 5 or 6 years similar to what
everyone here has related. And Parkinson's is like every other
disease. It is individual. It affects people in different ways.
If you ever looked at a fight tape of Muhammad or an
interview or a documentary, you know how he lit up the screen
and how he loved the camera. Now you see him sitting here with
his eyes closed. It is not because he is trying to block you
out, it is because Parkinson's made him photophobic to light.
His face does not love the camera like it used to.
In fact, I think the biggest thing that Parkinson's has
done is rob this man of his confidence which I think is just
absolutely horrible. I think we are being deprived of a lot of
things from this man and a lot of other people, but his day is
not like it used to be. It is very difficult for him to move
around. He is a prisoner in his body.
Senator Harkin. Of all the good that you have done,
Muhammad, around the globe, I still believe that you are one of
the greatest ambassadors of good will this country has ever
had. If I were President, I would be calling on you, I can tell
you that, even with Parkinson's. I think again the courage that
you show to people around the world who know you, this could
have a profound effect and will have a profound effect on
people. There are a lot of people around the globe who look
upon you, and rightfully so, as a great hero of theirs. They
may not have much hope for their lives, but you give them hope.
So, I encourage you, Muhammad, keep on and just keep on
fighting. You got it, man.
Well, Mrs. Ali, you quoted Dr. William Langston who said
sometimes you hit the point where it is time to focus.
Ms. Ali. That is correct.
Senator Harkin. And now is the time to focus.
I thank you all for being here. I will close by just saying
that, first, a disclaimer. We do not on this committee specify
what NIH has to do. We are not scientists. I am not a
scientist. I believe over my years here, though, I have
absorbed quite a bit. I am not an expert, though. But I have
been on this committee now 18 years, first under Lowell Weicker
and then Lawton Chiles. Then I was chairman, then Senator
Specter, and now I am back again as chair. Through those years,
we have seen great progress made through NIH. It really is the
crown jewel of the Federal Government, no doubt in my mind. And
I am proud that Senator Specter and I were able to work
together collaboratively to double the funding for NIH. So, I
do not feel within my purview or Senator Specter's or anyone
else to tell NIH put this money in this research, put this
money in that research.
But I am a public servant. I have to reflect what the
public wants. That is my oath of office. I also need to
translate to NIH what we hear here in this hearing room. Now,
scientists are doing their job. Our job is to try to help them
do their job, not in the way of explicitly telling them what to
do, but our telling them here is what we are hearing from the
public. Here is what we know on the record. Here is what
experts from different fields have told us. And it is the
interest of this subcommittee that funds NIH that you take this
into consideration and look at it in your decisions on how much
to put in funding different disease groups.
That is why last year some people say I stepped out of
bounds--but I do not believe so--in the language that I
inserted in with our funding bill on Parkinson's. Year after
year, under Senator Specter and last year under my
chairmanship, we kept seeing that needle move more and more
away from just the basics into actually something that needs to
be translated. So, we wanted and I wanted specifically to put
some very strong language in there not just to tell scientists
what to do but to tell them here is the sum and substance of
what we have heard here, not just me, but all the witnesses,
the experts, the other scientists in the field are saying. And
you need to act on this and come back and tell us what you are
going to do.
So, I think that is a proper role for us to play here and
we will continue to play that role. So, I will in drafting the
language on this bill again say to Dr. Zerhouni, who is now the
new head of NIH, that this is what we are hearing, that the
language I used last year was intended to let you know that
this committee feels very strongly that we need not just a
percentage increase, but we need to get as close as possible to
the research agenda put forward by the Parkinson's Action
Network. As close as possible.
And you have my word that language will be in there this
year.
In our oversight hearings, we will have again Dr. Penn and
the head of NIH down to ask what they are doing in this area,
because I believe this is what this committee has heard from
you and from other witnesses, that we need to move ahead
aggressively in this area.
So, again, I thank you all very much for being here. Joan,
I think thank you especially for your great leadership in this
area. You have been the driving force behind this. Actually,
you know, Joan Samuelson probably wears about a 5 shoe or 6
shoe, but I feel sometimes it is about a size 15 in the middle
of my back sometimes.
But it feels good because you are doing the right thing and
you keep us informed and advised. You keep pushing us. And that
is what you ought to be doing too. Keep on pushing us too.
Dr. Penn, thank you for your leadership there.
Muhammad Ali, Michael J. Fox, thank you so much for your
leadership, your inspiration. You have given us all this hope
and courage.
Don Schneider, see you back in Clinton. We are going to
lick this thing.
prepared statement and letter received
We have received the prepared statement of Senator Thad
Cochran and a letter from Do No Harm: The Coalition of
Americans for Research Ethics. They will be placed in the
hearing record.
[The statement and letter follow:]
Prepared Statement of Senator Thad Cochran
Mr. Chairman, thank you for conducting this hearing on Parkinson's
Disease research. Parkinson's Disease is a good example of how our
efforts to increase medical research funding are making a difference.
We began this effort in 1997 with the Morris K. Udall Parkinson's
Disease Research Act. Since that time, there has been impressive
progress in the effort to find a cure.
Important areas of this research include prevention, diagnosis and
treatment of Parkinson's. Another important development has been the
collaboration between NIH Institutes and researchers. We must explore
further how advances in imaging technologies can improve diagnosis and
treatment of Parkinson's. We must also consider such areas as the link
between environmental conditions and the disease. We can only address
many of these issues through greater NIH research collaboration.
I agree with a statement Michael J. Fox made several years ago that
``this is a winnable war''. I believe, however, it is only winnable if
we continue our investment in research. I thank the researchers and
patients here today for keeping us focused on how this investment will
help us win this war.
______
Letter from Do No Harm: The Coalition of
Americans for Research Ethics,
May 21, 2002.
Hon. Tom Harkin,
Chairman, Subcommittee for Labor, HHS and Education,
Senate Appropriations Committee, Washington, DC.
Dear Senator Harkin: I would like to submit this letter and
enclosed fact sheet as a written submission for your May 22 hearing on
Parkinson's disease. These are submitted on behalf of Do No Harm: The
Coalition of Americans for Research Ethics, a coalition of scientists,
researchers, bioethicists and others supporting adult stem cell and
other research avenues to cure disease that do not rely on the creation
and destruction of human life.
It is important to note how predictions have changed in less than a
year regarding the most promising avenues for Parkinson's research.
Last summer the Parkinson's Action Network urged Congress to
support federal funding of embryonic stem cell research, declaring:
``We need a medical rescue and we need it now. Scientists agree it is
possible this decade'' (PAN press release, July 17, 2001). Just a few
months later, however, PAN testified to the President's Council on
Bioethics that clinical benefits from this source are highly
uncertain--and that any benefits which do ultimately arrive may take
``another generation'' to help human patients (Statement of Elisabeth
Breese Brittin, Transcript of the President's Council on Bioethics,
January 18, 2002). This shift in prognosis is warranted by the very
disappointing results thus far from the use of embryonic stem cells.
These cells have produced some modest benefits in animal trials for
Parkinson's disease, but also shown a disturbing tendency to form
lethal tumors when placed in living animals. Thus they are a very long
way from being considered safe (let alone effective) for human clinical
trials. Use of stem cells from cloned embryos poses its own additional
problems and risks, due to the havoc wreaked by the cloning process
upon orderly gene expression and other factors.
Fortunately, there is also great reason for hope regarding this
disease. At the same time that timetables have been lengthened for
benefits from embryonic stem cells, timetables have been moved up for
benefits from adult stem cells and other alternatives. Recent clinical
trials have shown an almost complete reversal of Parkinson's symptoms
for one patient, using his own adult stem cells, and very promising
results for several other patients using donated adult retinal cells.
These avenues, as well as new advances in gene therapy and other
approaches, do provide reason to hope that we can indeed speak of a
cure for Parkinson's in this decade.
We hope Congress will take note of these new developments, which
provide a ``win-win'' situation for all involved in the stem cell
debate: A clear path to new treatments and perhaps cures, without
posing the moral and legal problems connected with embryo research and
cloning.
Sincerely,
Gene Tarne,
Communications Director.
Treating Parkinson's With Adult Stems Cell and Other Alternatives
in humans
Total Reversal of Symptoms Reported
Using adult neural stem cells, Dr. Michel Levesque, at the Cedars-
Sinai Medical Center in Los Angeles, reports a total reversal of
symptoms in the first Parkinson's patient treated. The patient, a 57-
year old former fighter pilot, is still without symptoms three years
after the adult neural stem cells were removed from his brain, coaxed
into becoming dopamine-producing cells, and then reimplanted. Because
the stem cells came from the patient, there was no need for
immunosuppression to overcome rejection. ``I think transplantation of
the patient's own neural stem cells and differentiated dopaminergic
neurons is more biologically and physiologically compatible--more
efficacious and more elegant,'' said Levesque. In addition to its use
for Parkinson's, the technique is under study for juvenile diabetes,
stroke, brain tumors, spinal cord injury, and other conditions.
Reference.--Results presented April 8th, at the meeting of the
American Association of Neurological Surgeons.
Retinal Cell Implants Improve Parkinson's
A team at Emory University School of Medicine has shown that
implanting retinal cells into the brains of people with advanced
Parkinson's disease can improve motor function by almost half,
according to a follow-up study of six patients. The team noted: ``We've
been following these six participants for over a year, and we've found
they've improved, on average, nearly 50 per cent in motor function.''
The retinal cells used were taken from deceased donors and grown in the
lab. The team is not using immunosuppressants.
Reference.--Result presented April 18 at the annual conference of
the American Academy of Neurology in Denver and reported in the New
Scientist, 18 April 2002.
N.B.--There are no clinical treatments for Parkinson's based on
cloning or embryonic stem cells.
in animals
Stimulating Adult Brain Stem Cells Decreases Parkinson's Symptoms
Injection of growth protein into brains of Parkinson's rats caused
their neural stem cells to grow, migrate to the site of damage, and
begin to replace missing nerve cells. Eighty percent (80 percent) of
the rats received a benefit from the treatment, with no tumor
formation.
Reference.--J. Fallon et al.; ``In vivo induction of massive
proliferation, directed migration, and differentiation of neural cells
in the adult mammalian brain,'' Proc. Natl. Acad. Sci. USA 97, 14686-
14691; December 19, 2000.
Progenitor Cells Reverse Severe Parkinson's Symptoms in Rats
Researchers at Chicago's Rush University report coaxing progenitor
cells from the brains of rats into becoming dopamine neurons to treat
Parkinson's disease. Led by Paul Carvey, the team discovered an
important ``shortcut'' to creating a more efficient, more reliable, and
safer source of stem cells with the ability to turn into specific
neurons or brain cells. This study is the first to identify the signal
that instructs stem/progenitor cells to become dopamine neurons. The
researchers watched the cells develop, and selected and grew cells that
were close to becoming neurons. They then grafted the cells into brains
of Parkinson's rats, effectively curing the animals' severe Parkinson
symptoms. The ability to select and grow large numbers of adult stem
cells that would become neurons also has the potential to revolutionize
the treatment of Alzheimer's disease, multiple sclerosis and numerous
other diseases and disorders of the brain and nervous system.
Reference.--Results reported at the Experimental Biology Meeting in
New Orleans, April 2002.
N.B.--In contrast to these animal studies using adult stem cells, a
widely publicized study showed Parkinson's rats injected with mouse
embryonic stem cells receiving a modest benefit for just over 50
percent of the rats, but one-fifth (20 percent) of the rats died of
brain tumors caused by the embryonic stem cells.
Reference.--L.M. Bjorklund et al.; ``Embryonic stem cells develop
into functional dopaminergic neurons after transplantation in a
Parkinson rat model,'' Proc. Natl. Acad. Sci. USA 99, 2344-2349; Feb
19, 2002 (published online Jan 8, 2002)
Gene Therapies Treat Parkinson's in Rats, Monkeys
The injection of two corrective genes into a specific brain region
generated significant restoration of normal limb movement in rats with
Parkinson's disease. Limb impairments were completely reversed in rats
that had near-total Parkinsonian lesions on only one side of the brain,
meaning that some of their dopamine-producing cells remained intact.
But even in the rats with complete destruction of dopamine-producing
cells, the delivery of gene therapy resulted in a limited amount of
restored motor function. ``We anticipate gene therapy will offer a way
to help patients with Parkinson's disease live many years longer free
of disabling symptoms,'' the researchers noted.
Reference.--D. Kirik et al.; ``Reversal of motor impairments in
parkinsonian rats by continuous intrastriatal delivery of L-dopa using
rAAV-mediated gene transfer,'' Proceedings of the National Academy of
Sciences USA 99, 4708-4713; April 2, 2002.
A Japanese research team has demonstrated delayed delivery of gene
therapy can provide significant recovery from Parkinson's symptoms.
Four weeks after inducing Parkinson's damage in their brains, rats were
given an injection of a gene vector which produced a growth protein
call ``glial cell line-derived neurotrophic factor'' (GDNF). The
animals showed remarkably higher levels of dopamine secretion and
significant behavioral recovery, even up to 20 weeks following the
injection.
Reference.-- Wang L. et al.; ``Delayed delivery of AAV-GDNF
prevents nigral neurodegeneration and promotes functional recovery in a
rat model of Parkinson's disease,'' Gene Therapy 9, 381-389; March
2002.
Treatment with three gene therapy vectors has shown behavioral
recovery in Parkinson's monkeys. The treatment resulted in remarkable
improvement in manual dexterity and restoration of motor functions,
with the behavioral recovery persisting for over 10 months in one case.
The scientists say that this triple gene therapy method may offer a
potential therapeutic strategy for Parkinson's disease.
Reference.--S. Muramatsu S. et al., ``Behavioral recovery in a
primate model of Parkinson's disease by triple transduction of striatal
cells with adeno-associated viral vectors expressing dopamine-
synthesizing enzymes,'' Human Gene Therapy 13, 345-354; February 10,
2002.
CONCLUSION OF HEARING
Senator Harkin. Thank you all very much for being here,
that concludes our hearing.
[Whereupon, at 11:23 a.m., Wednesday, May 22, the hearing
was concluded, and the subcommittee was recessed, to reconvene
subject to the call of the Chair.]
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