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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

(

Available via the World Wide Web: http://www.access.gpo.gov/congress/senate
(II)

COMMITTEE ON APPROPRIATIONS

ROBERT C. BYRD, West Virginia, Chairman

DANIEL K. INOUYE, Hawaii

ERNEST F. HOLLINGS, South Carolina

PATRICK J. LEAHY, Vermont

TOM HARKIN, Iowa

BARBARA A. MIKULSKI, Maryland

HARRY REID, Nevada

HERB KOHL, Wisconsin

PATTY MURRAY, Washington

BYRON L. DORGAN, North Dakota

DIANNE FEINSTEIN, California

RICHARD J. DURBIN, Illinois

TIM JOHNSON, South Dakota

MARY L. LANDRIEU, Louisiana

JACK REED, Rhode Island

TED STEVENS, Alaska

THAD COCHRAN, Mississippi

ARLEN SPECTER, Pennsylvania

PETE V. DOMENICI, New Mexico

CHRISTOPHER S. BOND, Missouri

MITCH MCCONNELL, Kentucky

CONRAD BURNS, Montana

RICHARD C. SHELBY, Alabama

JUDD GREGG, New Hampshire

ROBERT F. BENNETT, Utah

BEN NIGHTHORSE CAMPBELL, Colorado

LARRY CRAIG, Idaho

KAY BAILEY HUTCHISON, Texas

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

SUBCOMMITTEE ON DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND

EDUCATION, AND RELATED AGENCIES

TOM HARKIN, Iowa, Chairman

ERNEST F. HOLLINGS, South Carolina

DANIEL K. INOUYE, Hawaii

HARRY REID, Nevada

HERB KOHL, Wisconsin

PATTY MURRAY, Washington

MARY L. LANDRIEU, Louisiana

ROBERT C. BYRD, West Virginia

ARLEN SPECTER, Pennsylvania

THAD COCHRAN, Mississippi

JUDD GREGG, New Hampshire

LARRY CRAIG, Idaho

KAY BAILEY HUTCHISON, Texas

TED STEVENS, Alaska

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
(III)

CONTENTS

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

(1)

PARKINSON’S DISEASE RESEARCH

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.
2

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.
3

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.
4

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.
5

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
6

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 famil-
7

ial 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.
8

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, reexamine 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 in-
9

vestigator-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 surgicallyimplanted 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.
10

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.
11

—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
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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.
13

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.
14

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
15

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 (Ldopa) 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.
16

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
17

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
18

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-diag-
19

nosis, 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
20

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 di-
21

rection 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
22

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
23

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.
24

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
25

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 copilot, 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 Par-
26

kinson’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 oppor-
27

tunities 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
28

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
29

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 higherrisk, 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
30

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:]
31

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.
32

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
33

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 61⁄2 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 fre-
34

quent, 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.
35

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 Par- kinson’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
36

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 Ldopa 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
37

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 Parkin-
38

son’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 in-
39

novative 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.
40

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
41

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.
42

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
43

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.
44

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 dopamineproducing 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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