[Senate Hearing 107-99]
[From the U.S. Government Publishing Office]
S. Hrg. 107-99
MUSCULAR DYSTROPHY
=======================================================================
HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED SEVENTH CONGRESS
FIRST SESSION
__________
SPECIAL HEARING
FEBRUARY 27, 2001--WASHINGTON, DC
__________
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COMMITTEE ON APPROPRIATIONS
TED STEVENS, Alaska, Chairman
THAD COCHRAN, Mississippi ROBERT C. BYRD, West Virginia
ARLEN SPECTER, Pennsylvania DANIEL K. INOUYE, Hawaii
PETE V. DOMENICI, New Mexico ERNEST F. HOLLINGS, South Carolina
CHRISTOPHER S. BOND, Missouri PATRICK J. LEAHY, Vermont
MITCH McCONNELL, Kentucky TOM HARKIN, Iowa
CONRAD BURNS, Montana BARBARA A. MIKULSKI, Maryland
RICHARD C. SHELBY, Alabama HARRY REID, Nevada
JUDD GREGG, New Hampshire HERB KOHL, Wisconsin
ROBERT F. BENNETT, Utah PATTY MURRAY, Washington
BEN NIGHTHORSE CAMPBELL, Colorado BYRON L. DORGAN, North Dakota
LARRY CRAIG, Idaho DIANNE FEINSTEIN, California
KAY BAILEY HUTCHISON, Texas RICHARD J. DURBIN, Illinois
MIKE DeWINE, Ohio TIM JOHNSON, South Dakota
MARY L. LANDRIEU, Louisiana
Steven J. Cortese, Staff Director
Lisa Sutherland, Deputy Staff Director
James H. English, Minority Staff Director
------
Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
ARLEN SPECTER, Pennsylvania, Chairman
THAD COCHRAN, Mississippi TOM HARKIN, Iowa
JUDD GREGG, New Hampshire ERNEST F. HOLLINGS, South Carolina
LARRY CRAIG, Idaho DANIEL K. INOUYE, Hawaii
KAY BAILEY HUTCHISON, Texas HARRY REID, Nevada
TED STEVENS, Alaska HERB KOHL, Wisconsin
MIKE DeWINE, Ohio PATTY MURRAY, Washington
MARY L. LANDRIEU, Louisiana
ROBERT C. BYRD, West Virginia
(Ex officio)
Professional Staff
Bettilou Taylor
Mary Dietrich
Jim Sourwine
Ellen Murray (Minority)
Administrative Support
Correy Diviney
Carole Geagley (Minority)
C O N T E N T S
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Page
Opening statement of Senator Arlen Specter....................... 1
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.. 2
Prepared statement........................................... 4
Statement of Senator Paul Wellstone.............................. 10
Statement of Lee Sweeney, Ph.D., scientific director, Parent
Project Muscular Dystrophy..................................... 11
Prepared statement........................................... 12
Statement of Leon Charash, M.D., chairman, Medical Advisory
Committee, Muscular Dystrophy Association...................... 16
Prepared statement........................................... 17
Statement of Senator Larry Craig................................. 18
Statement of Donavon Decker, limb-girdle muscular dystrophy
patient, Huron, South Dakota................................... 21
Prepared statement........................................... 22
Statement of Patricia Furlong, president, Parent Project Muscular
Dystro-
phy............................................................ 23
Prepared statement........................................... 25
Statement of Chris Rosa, Ph.D., member, Muscular Dystrophy
Association board of directors, member, President's Committee
on Employment of People With Disabilities...................... 28
Prepared statement........................................... 29
Statement of Jerry Lewis, international entertainer and national
chairman, Muscular Dystrophy Association....................... 32
Prepared statement........................................... 34
Prepared statement of Jeff Baxter................................ 37
MUSCULAR DYSTROPHY
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TUESDAY, FEBRUARY 27, 2001
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 9:30 a.m., in room SH-216, Hart
Senate Office Building, Hon. Arlen Specter (chairman)
presiding.
Present: Senators Specter and Craig.
Also present: Senator Wellstone.
Opening statement of Senator Arlen Specter
Senator Specter. We have delayed slightly by just a few
minutes the opening of this hearing so that I could go into the
anteroom and brief the witnesses who are going to testify here
today. This is a hearing of the Appropriations Subcommittee for
Labor, Health, Human Services, and Education, and this is a
hearing in a long line of hearings where we focus on
particularly distressing ailments.
Today, as you know, it is muscular dystrophy. At other
times we have special hearings on amyotrophic lateral
sclerosis, on Alzheimer's, on cancer, on Parkinson's, and we do
this at the request of the various groups. Today, the hearing
has been scheduled at the specific request of the Parent
Project Muscular Dystrophy as part of their first annual
legislative conference. Approximately 110 Parent Project
Muscular Dystrophy parents are going to participate in the
conference, and there are 20 young entertainers participating
in the Kids for Kids Project to focus on this particularly
disabling childhood ailment.
Muscular dystrophy refers to a group of genetic diseases
characterized by progressive muscle weakness and control of
movement, frequent falls, problems walking, eyelid-drooping,
skeletal and muscle deformities. The research efforts on
muscular dystrophy have been very, very extensive.
On a bipartisan basis, together with Senator Tom Harkin,
Democrat of Iowa, this subcommittee has taken the lead to
vastly increase the funding for the National Institutes of
Health. Four years ago, the funding level was about $12
billion. Now it is in excess of $20 billion, and we are moving
on what is a glide path to try to double NIH funding over a 5-
year period, and we have set a very ambitious mark this year to
try to add $3.6 billion which is our hope, perhaps more
specifically our expectation, and it has been a real battle,
because the funding for the National Institutes of Health comes
from Health and Human Services generally, where there are so
many other vital programs, and it is also lumped together with
the Department of Education, and there is no priority in
America higher than education, and also with Labor, with
workers' safety, so we have our work cut out for us.
I frequently say that the National Institutes of Health are
the crown jewel of the Federal Government, and then I quickly
add, perhaps the only jewel of the Federal Government. That is
with the exception, of course, of those assembled here in this
hearing room today.
One item that I want to comment about is our continuing
effort to promote research on stem cells. Stem cells burst on
the national scene in November of 1998, and this subcommittee
then moved very quickly into a series of hearings. We had some
seven hearings with a view to eliminate the prohibition against
using Federal funds to extract stem cells from embryos.
Embryos are created, as you may know, for in vitro
fertilization, and they are to be discarded. They are not going
to be used. I would never advocate taking an embryo that could
produce a live person for research, but when they are going to
be discarded, it's a question of either having them used for
nothing, or having them used to save lives. They are a
veritable fountain of youth. These stem cells can be
substituted for cells in the body. They are especially helpful
on Parkinson's already, with the projection of a cure within 5
years, and on spinal cord problems, and they may be useful on
muscular dystrophy as well. The sky really is the limit.
At the moment there are grants pending in the Department of
Health and Human Services, where it is now lawful, according to
an opinion by the General Counsel, to use Federal funds on stem
cell research after they have been extracted from the embryos,
and that is something which I personally feel very strongly
about ought to be maintained, and we really ought to eliminate
the limitations. This is a matter for the scientists, not a
matter for the Congress, in my opinion.
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 Specter. We will now move to our first witness. Dr.
Audrey S. Penn, Acting Director, National Institute of
Neurological Disorders and Stroke. Dr. Penn comes to this
position having served as Deputy Director of the Institute. She
is a member of the American Academy of Neurology and the
American Association for the Advancement of Sciences, past
president of the American Neurological Association. She
received her M.D. from Columbia and her B.A. from Swarthmore,
parenthetically a suburb of Philadelphia.
Welcome, Dr. Penn. We look forward to your testimony.
Dr. Penn. Thank you, Mr. Chairman. I am here to discuss the
muscular dystrophies with you. As an academic neurologist and
investigator working on neuromuscular diseases, and now----
Senator Specter. I am told we have some 20 people outside
who cannot gain entry. They are welcome to come in, and they
can be Senators for a day. For a higher rank they can be
staffers for a day, sitting behind the Senators' seats, but if
the guards would let all the people in, we have plenty of room
here.
Dr. Penn, please proceed.
Dr. Penn. Yes, sir.
I have been well aware of the muscular dystrophies and the
problems they present. As you stated, they are inherited,
degenerative diseases of skeletal muscle which result in
progressive muscle weakness. The muscles involved vary. The FSH
dystrophy, facioscapulohumeral involves face, shoulders, and
upper arms, limb girdle, shoulders and hips, oculopharyngeal,
eyes and swallowing. They also vary in age of onset, rate of
progression, degree of ultimate disability, pattern of
inheritance, and the specific genes which are missing or
defective.
Now, the diagnostic tests used are the same: clinical
examination, electrophysiological testing, and measurement of
muscle-derived enzyme in serum. This morning, I will focus on
Duchenne muscular dystrophy.
Duchenne strikes males, starting in infancy, when it may be
clinically suspected either by an extremely high serum enzyme,
or subtle weakness as children start to walk. There is rapid
progression. On average a wheelchair is needed at about age 12.
Early in the process, there are obvious signs of regeneration
of muscle, but degeneration progressively outpaces
regeneration.
After years of work, much of which was funded also by MDA,
the gene was identified, then its protein product, named
dystrophin. Now, dystrophin is a giant protein which provides
structural support to a critical complex of muscle membrane
proteins, and links the internal muscle cell structure to the
membrane surface. The Becker dystrophy, a milder form of
Duchenne, reflects a defective rather than a missing dystrophin
gene. It is less destructive, and slower to progress.
The relatively numerous and heterogeneous limb girdle
dystrophies reflect the loss of other proteins at that same
dystrophin complex, suggesting that the loss of stability of
this set of proteins is critical to many of the dystrophies.
Now, there is still no cure for any of the muscular
dystrophies. Physical therapy, tendon-lengthening to prolong
walking and measures to preserve lung and heart function may
all improve the quality of life. Corticosteroid usage at
certain stages may help, but the side effects are especially
troublesome in growing children.
There have also been continuous efforts to replace that
gene since it was first identified in 1987, and scientists
today are concentrating on new strategies. Studies of a mouse
model indicate that the use of viruses as vectors to carry
genes into muscle cells is possible. However, the dystrophin
gene is so big, it does not fit inside usable viral vectors,
and vectors may also trigger an immune response.
Other innovative approaches currently being investigated in
the mouse include direct administration of DNA, the use of
trimmed-down minigenes, strategies which can alter how the gene
makes the protein, and replacement of dystrophin with a similar
but smaller protein found in a very specialized region of the
muscle membrane. Utrophin can fit inside usable viral vectors,
and can restore strength in mice. In mice which carry a
dystrophin mutation that causes an erroneous genetic signal to
stop making protein, a specific type of antibiotic can override
the signal. A similar mutation is found in about 15 percent of
children with Duchenne, and we are currently testing gentamycin
in clinical trials.
All of this contrasts with the autosomal dominant FSH
dystrophy, in which both men and women are affected. It may be
hard to discern weakness by inspection or exam in some, while
others are in wheelchairs. Even after the revolution on
molecular genetics and over 12 years of work, we have still
identified only the chromosomal region which is deleted in FSH.
The specific gene has not been identified. The deletion
probably acts indirectly on neighboring genes.
NIH Institutes, with the Parent Project for Muscular
Dystrophy, organized a workshop last spring to address possible
therapeutic approaches for Duchenne, and a second workshop on
FSH organized by NIH with the FSH Society focused on that
disease.
To follow up on these workshops, we have set aside funds,
and we have called for new applications. We value our
relationships with all of the voluntary organizations who work
so hard to move ahead and cure these diseases, and we want to
recognize their contributions: the MDA, which for years under
the tireless efforts of Jerry Lewis has fostered research on
muscular dystrophy, the Parent Project, which has brought a
renewed sense of urgency to the field, and the equally
dedicated FSH Society.
We believe we achieve results faster when we partner with
these organizations. We dedicate ourselves to ensuring that the
best science and scientists tackle these disorders, and put
research funds to the best possible use to begin effective
therapies.
PREPARED STATEMENT
Mr. Chairman, I appreciate the opportunity to discuss these
disorders, which have long been a concern of mine, and I am
pleased to respond to any questions you may have.
[The statement follows:]
Prepared Statement of Audrey S. Penn
Mr. Chairman, Ranking Member Senator Harkin, and Members of the
Subcommittee, I am Dr. Audrey Penn, Acting Director of the National
Institute of Neurological Disorders and Stroke. I am here to discuss
with you the muscular dystrophies. I have been actively involved with
this group of diseases throughout my career as a physician and
scientist, working in academia, with voluntary organizations, and at
the National Institutes of Health.
WHAT ARE MUSCULAR DYSTROPHIES?
The muscular dystrophies are a group of diseases which weaken the
skeletal muscles that we use to move voluntarily. These disorders vary
in their age of onset, in severity and in the pattern of which muscles
are affected. All forms of muscular dystrophy, however, grow worse as
muscles progressively degenerate. In some types of muscular dystrophy,
the heart, the gastrointestinal system, endocrine glands, the skin, the
eyes and other organs may be affected. All of the muscular dystrophies
are genetic disorders, although the types of inheritance vary, and
Duchenne muscular dystrophy, the most common and best known of the
childhood muscular dystrophies, often arises from new mutations.
CAN WE TREAT MUSCULAR DYSTROPHIES?
Research has revealed most--but not yet all--of the gene defects
that cause the different forms of muscular dystrophy. Unfortunately,
the life expectancy and quality of life for people with muscular
dystrophy have not improved substantially since those discoveries.
There is still no specific treatment that can stop or reverse the
progression of any form of muscular dystrophy. For Duchenne muscular
dystrophy, corticosteroids may help, but have side effects that can be
especially troubling with children. Symptomatic treatment, though not
able to stop the disease process, may improve the quality of life for
some people with muscular dystrophies, through physical therapy,
wheelchairs and braces used for support, corrective orthopedic surgery,
and drugs.
The failure so far to produce a definitive therapy for any form of
muscular dystrophy reflects the difficulty of the problems that we must
confront to cure these diseases. Some of these problems are unique to a
particular type of muscular dystrophy, some common to all muscular
dystrophies, and others are shared by many genetic disorders. The
National Institute of Neurological Disorders and Stroke (NINDS) and the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) lead efforts of several components of NIH against these
diseases. The shared responsibility recognizes the value that various
medical specialties and disciplines bring to research and treatment.
The muscular dystrophies affect many aspects of physiology, benefit
from a wide range of fundamental biological research, and require
exploration of diverse diverse strategies for treatment. What is most
encouraging is the range of scientific approaches that research is
bringing to bear on these diseases. Molecular biology has given us a
foothold to understand what goes wrong. To examine the list of
therapies being explored for the muscular dystrophies is tantamount to
taking a tour through the most active frontiers of modern medicine,
including gene therapy, cell replacement, and innovative approaches to
drug development.
Time will not allow me to describe all forms of muscular dystrophy.
I will discuss three common types--myotonic muscular dystrophy,
fascioscapulohumeral (FSH) muscular dystrophy and Duchenne/Becker
muscular dystrophy--and try to make some general points along the way.
MYOTONIC MUSCULAR DYSTROPHY
Myotonic muscular dystrophy (MMD) is probably the most common adult
form of muscular dystrophy, partly because people with this disorder
can live a long life, with variable but slowly progressive disability.
Myotonia refers to impaired muscle relaxation which is associated with
MMD along with muscle wasting and weakness. This form of muscular
dystrophy affects many body systems in addition to skeletal muscles.
These include the heart, endocrine organs, eyes, and gastrointestinal
tract.
Myotonic muscular dystrophy follows an autosomal dominant pattern
of inheritance. This means that the disorder can occur in either sex
when a person inherits a single defective gene from either parent. The
gene defect that causes MMD is a triplet repeat expansion in the
untranslated region of a gene that encodes a protein kinase (DM-PK). To
attempt to translate this into English: the inherited gene defect
arises from a long repetition of a three-letter ``word'' in the part of
the genetic code that carries the instructions for making a protein.
The protein is one of a class called ``kinases'' that help regulate the
function of other proteins. In this case the ``word'' is not in the
part of the gene that specifies the makeup of the protein itself, but
in a region that may help control when the gene is turned on and off.
We don't yet understand how this genetic defect leads to muscle
degeneration, but the ``triplet repeat'' mechanism has now been found
in at least 15 other disorders. Scientists have found some clues, both
for myotonic dystrophy and triplet repeat disorders in general, and
research is continuing. The fact that the repetition in the genetic
code tends to get longer with each generation explains the phenomenon
of ``anticipation'' in which the disease shows itself earlier and more
severely in each generation.
FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
Facioscapulohumeral muscular dystrophy (FSHD) initially affects
muscles of the face (facio), shoulders (scapulo), and upper arms
(humeral) with progressive weakness. Symptoms usually develop in the
teenage years. Life expectancy is normal, but some affected individuals
become severely disabled. The pattern of inheritance is, like myotonic
muscular dystrophy, autosomal dominant, but the underlying genetic
defect is poorly understood. Most cases are associated with a deletion-
that is, a missing piece of chromosome-near the end of chromosome #4.
These deletions don't appear to disrupt a particular gene, but may
affect the activity of nearby genes. This complicates the search for
the relevant gene and suggests a novel mechanism may be involved.
In recent months, NIAMS has led NIH in a number of important steps
to stimulate and support further work on this poorly understood form of
muscular dystrophy. These include:
Research conference.--In May 8-9 of 2000, the NIAMS, together with
the NINDS, the NIH Office of Rare Diseases, the FSH Society, Inc., and
the Muscular Dystrophy Association of America, co-sponsored a
scientific conference on the cause and treatment of FSHD. Researchers
from the United States, Canada, Europe, South America, and Asia met on
the NIH campus in Bethesda, Maryland, to share their latest findings
and identify exciting directions for future studies of this disease.
The recommendations that emerged from the conference fall into several
categories, including: efforts to enhance our understanding of the
molecular processes and tissue changes associated with FSHD; ways to
explore possible therapies to treat the disorder; and strategies to
promote the establishment of population-based studies of the disease,
as well as needed research resources. NIH is using these
recommendations as a guide in developing new program initiatives
related to FSHD and other muscular dystrophies. A summary of the
Workshop is available on the NIAMS web at: http://www.nih.gov/niams/
reports/fshdsummary.htm.
Research registry.--In September of 2000, the NIAMS and the NINDS
funded a research registry for FSHD and myotonic dystrophy. The long-
term goal of the registry is to facilitate research in FSHD and
myotonic dystrophy by serving as a liaison between families affected by
these diseases who are eager to participate in specific research
projects, and investigators interested in studying these disorders. The
registry, based at the University of Rochester, will recruit and
classify patients, and store medical and family history data for
individuals with clinically diagnosed FSHD and myotonic dystrophy.
Scientists will be provided with statistical analyses of the registry
data, as well as access to registry members who have agreed to assist
with particular research studies. The national registry will serve as a
resource for scientists seeking a cure for these diseases, in addition
to enhancing research to understand what changes occur in muscular
dystrophy.
Research solicitations.--In November of 2000, the NIAMS and the
NINDS jointly issued a request for applications for exploratory
research on FSHD. This announcement is designed to encourage research
proposals using creative, novel, potentially high risk/high payoff
approaches that could produce innovative advances in this field.
Successful projects may include feasibility studies, clinical protocol
planning, and efforts to incorporate new disciplines and technologies
into the study of FSHD. In developing this solicitation, the NIH built
on the insights we gained from the scientific conference cited above.
Based on that conference, we have focused this new request for research
proposals on issues related to improving our understanding of the
origins of this disease and how to characterize its molecular basis.
Among other areas, such projects could include studies looking at
changes in muscle as FSHD develops; exploring the role of inflammation
in this disease; and creating new models of FSHD that could facilitate
the eventual development of effective therapies.
In January of 2001, NIAMS and NINDS partnered again to issue a
program announcement with funds set aside to support research on
understanding and developing therapies for the muscular dystrophies,
including FSHD. This solicitation is described in the following
discussion of Duchenne muscular dystrophy discussion.
DUCHENNE AND BECKER MUSCULAR DYSTROPHY
Duchenne muscular dystrophy (DMD) is the most common childhood form
of muscular dystrophy, affecting approximately 1 in 3,000 male births.
About one third of cases reflect new mutations and the rest are
familial. Because inheritance is X-linked recessive, DMD affects
primarily boys, though girls and women who carry one defective gene may
show some mild symptoms.
DMD is a particularly devastating and lethal form of muscular
dystrophy. When the body's attempts to regenerate muscle cannot keep up
with the destructive process, muscle wasting and progressive weakness
result. DMD usually becomes evident when children begin to walk. Boys
typically require a wheelchair by age 10 to 12, and usually die in late
teens or early 20's. Becker muscular dystrophy (BMD) is a less severe
but closely related disease. DMD results from an absence of the protein
dystrophin, and BMD reflects a partly functional version of the same
protein.
Research conference.--To explore what NIH can do to develop
effective therapies for DMD and BMD, the NINDS, the NIAMS, and the NIH
Office of Rare Diseases (ORD), working together with the Parent Project
for Muscular Dystrophy held a ``Workshop on Therapeutic Approaches for
Duchenne Muscular Dystrophy'' on May 15 and 16, 2000, on the NIH campus
in Bethesda, Maryland. An international group of experts participated
in this meeting along with representatives from United States and
European muscular dystrophy associations and NIH staff. On May 17,
following the Workshop, the scientific organizers, topic leaders, and
NIH program directors met to summarize the discussion and formulate
future research priorities. A summary of the workshop is posted on the
NINDS websites at: http://www.ninds.nih.gov/news__and__events/
dmdmtngsummary.htm.
Understanding the disease.--More than 15 years ago, researchers
supported by the NIH and the Muscular Dystrophy Association identified
the gene for dystrophin that, when defective, causes DMD and BMD. The
identification of the dystrophin gene stimulated research that provided
new insights and directions for research on the biology of muscle and
the mechanisms of disease, as evident in thousands of high quality
scientific publications and several promising leads for developing new
therapies.
One challenge the dystrophin gene presents is its enormous size.
The gene is the largest gene yet identified in humans. Most vectors
(usually modified viruses) available for gene replacement cannot
incorporate a gene of this magnitude. The size probably also
contributes to the high rate of new mutations in the gene and to the
large number of different mutations that can occur within the gene.
Definitive therapy may require precise knowledge of the particular gene
defect in each patient.
The dystrophin protein was unknown before the discovery of its link
to DMD. Subsequent studies have revealed that dystrophin is part of a
complex structure involving several other protein components. The
``dystrophin-glycoprotein complex'' helps anchor the contents of muscle
cells through the cells' outer enclosing membrane to the material in
which muscle cells are embedded. Defects in this assembly lead to
structural problems that can disrupt the integrity of the outer
membrane of muscle cells, resulting eventually in degeneration. One of
the most remarkable spin-offs from the elucidation of the complex has
been clarification of the interrelationships among DMD and other forms
of muscular dystrophy. Several other forms of muscular dystrophy, whose
relationships to DMD were obscure, result from mutations in other
protein components of the same dystrophin-glycoprotein complex. These
include several forms of limb girdle muscular dystrophy, named for the
characteristic pattern of muscle weakness. Research to more fully
understand the normal and abnormal functions of the dystrophin complex,
and of other proteins closely related to dystrophin, is ongoing, and
evidence is accumulating that these proteins play important roles in
the brain as well as in muscles.
Therapeutic approaches.--Several new approaches have emerged for
developing therapies to stop or reverse muscle degeneration in Duchenne
muscular dystrophy. All of these strategies rely upon increased
understanding of the underlying biology of the disease. However, one
point made at the May workshop is the extent to which novel therapeutic
strategies for DMD arise from research that is not focused on muscular
dystrophy, muscle biology, or even therapeutics in general.
Logically, the simplest approach to treating DMD might seem to be
to supply a good copy of the defective gene. An important advantage in
studying DMD is the availability of the mdx mouse which is a useful
model of the human disease. Results in mice with the same gene defect
as DMD show that modified virus ``vectors,'' such as the adeno-
assocated virus, can carry the therapeutic genes into muscle cells and
partially reverse the disease. Recent experiments have also shown that
a genetically engineered ``mini-dystrophin,'' while much smaller than
the natural form, seems able to carry out its essential functions.
However, considerable advances are needed to make gene replacement
workable for children with MD. The technology of gene replacement is
just beginning to yield clinical success in some of the simplest
diseases to treat. Treating DMD presents special problems not only
because of the large size of the gene, but also due to the need to
deliver the gene reliably and safely to muscle cells throughout the
body. Improving the delivery of genes to muscle, optimizing the control
elements that regulate the activity of therapeutic genes, and
minimizing immunological and other potential safety problems are on-
going areas of research. The first preliminary gene replacement trials
for any form of muscular dystrophy have been designed by MDA for a form
of limb girdle muscular dystrophy caused by a defect in a component of
the dystrophin-glycoprotein complex.
Several other approaches to counteracting the gene defect, besides
gene transfer by viral vectors, also show promise for DMD. The use of
``naked DNA'' is one approach under investigation for several diseases
that may be applicable to DMD. Another approach uses chimeraplasts.
These specifically designed synthetic molecules are hybrids of DNA and
RNA that can guide the muscle cells' own repair machinery to correct
some types of defect in the dystrophin gene. ``Antisense'' nucleotides
are another type of synthetic molecule that has therapeutic potential.
These molecules, which are designed to bind specifically to certain
parts of genetic material, alter how the cells' internal machinery
reads a gene to make protein, thus compensating for certain types of
defects in dystrophin. Another strategy uses aminoglycoside
antibiotics. Some children with DMD (perhaps 15 percent) carry a
mutation in the dystrophin gene that creates an erroneous DNA code
signal to stop making the protein. Dr. Sweeney, who will also testify
today, did experiments in mice with the same types of errors in
dystrophin and found that antibiotics can cause the protein
synthesizing machinery to ignore stop signals and allow muscle cells to
make enough dystrophin. Gentamicin, an antibiotic of this type, is now
being tested in clinical trials for DMD in children.
Finally, drug therapy for DMD has also been a focus of research
efforts. One approach has used high-throughput screening (HTS) to try
to find drugs that increase the muscle production of another protein,
utrophin, that can help compensate for the loss of dystrophin. High
throughput screening employs robotics and miniaturized assays (tests)
to screen thousands of chemical compounds quickly to find leads for
further drug development. Other pharmacological research areas of
continued interest for DMD relate to the use of corticosteroids in the
disease and to strategies informed by increased understanding of
immunology and its relation to DMD.
Solicitations.--As noted above, in January 2001, NINDS and NIAMS
issued a PA-S (program announcement with set-aside) entitled
``Therapeutic and pathogenic approaches for the muscular dystrophies''
to encourage research in areas highlighted as priorities at the DMD and
FSHD workshops and in areas important for other forms of muscular
dystrophy. The PA-S, unlike a regular PA, sets aside funds ($5 million)
for the purpose of this research. Unlike an RFA (request for
applications), this mechanism does not restrict researchers to a single
deadline for proposals. Unsuccessful applicants are encouraged to
reapply after improving their proposals based on the suggestions of
scientists on peer review panels.
Several other actions of NINDS, NIAMS and other components of NIH
address priorities for muscular dystrophy research that also have
implications for other disorders. These include extensive efforts,
through workshops, solicitations, and other actions, to promote new
technological approaches, such as gene replacement, and to encourage
exploratory grants from researchers not currently working in the field.
Planned workshops will also focus on issues such as review of steroids
for treatment of DMD and clinical trial design for testing of these
drugs and issues in screening of newborns for eventual identification
of DMD when a treatment is available. NINDS has also placed an
increased emphasis on expediting clinical trials for neurological
disorders. In addition to grant mechanisms for pilot trials and
planning of large trials, the Institute is enhancing its ability to
work with researchers to design and conduct clinical trials. NIAMS is
also supporting planning grants for clinical trials, including one on
myotonic dystrophy.
In recent years, NIAMS and NINDS have also worked together to
strengthen NIH Intramural research in muscle biology and disease. The
Institutes have recruited outstanding scientists to lead research
programs in this area. One consequence, for example, is that the
resources of the NIH Intramural program have been used to expedite
clinical trials of gentamicin therapy of DMD and to discuss the
implications of findings so far with this strategy.
CONCLUDING REMARKS
The muscular dystrophies impose enormous burdens on people with
these disorders and on their families. We at NIH recognize the need to
target increased efforts against the muscular dystrophies. We are doing
so through the workshops, then following up with targeted solicitations
for applications, including set-aside funds designed to recruit new
investigators to the field, and through other efforts in both
extramural and intramural programs that I have cited above. The
promising opportunities for developing therapies build upon what we
have learned about these disorders, and we must continue to learn more
even as we move toward testing the best candidate therapies. It is also
worth noting that the therapeutic strategies we are now investigating
arose from research not targeted to these diseases, so we must maintain
a broad front of progress in neuroscience, muscle disorders, and
biology generally.
Finally, we at the NIH want to recognize the contributions of the
foundations represented here today--the Muscular Dystrophy Association,
which for years with the tireless efforts of Jerry Lewis has fostered
research in muscular dystrophy and other neuromuscular diseases, and
the Parent Project, which has brought a renewed sense of urgency to the
field. The NINDS stands ready and able to work in partnership with
these organizations and others in the United States and abroad to take
the lead in a new strategy that will build on all we have learned in
the past 15 years and bring effective treatment for muscular dystrophy
patients. We appreciate your efforts in increasing funding for NIH
overall and the NINDS in particular, and we dedicate ourselves to the
task of putting this money to the best possible use in helping patients
with these diseases.
Mr. Chairman, I appreciate the opportunity to discuss these
disorders, which have long been a major concern of mine, and I am
pleased to respond to any questions you may have.
Senator Specter. Thank you, Dr. Penn. Will the folks who
just came in on the center aisle, you are welcome to come up
front and to sit on the chairs for the staffers, or to sit in
the Senators' chairs, so why don't you walk forward, because
you are obstructing the views of some.
Dr. Penn, could you give us an idea as to what the
increases have been on the National Institute for Neurological
Disorders, say, in the last 4 years?
Dr. Penn. Yes, sir. We have received increases in fiscal
year 2001 of 14.2 percent over fiscal year 2000; in fiscal year
2000, 14 percent over fiscal year 1999; in fiscal year 1999,
15.6 percent over fiscal year 1998; and in fiscal year 1998,
7.4 percent over fiscal year 1997.
Senator Specter. And what is the total funding which is now
available for the national institute?
Dr. Penn. In fiscal year 2001 our appropriation is $1.176
billion.
Senator Specter. And in absolute dollars, what was the
increase last year, up to that figure?
Dr. Penn. Our increase from fiscal year 1999 to fiscal year
2000 was $126 million.
Senator Specter. Well, that is a very substantial increase.
Dr. Penn. Yes, sir.
Senator Specter. Let me ask you a highly dangerous
question. Are you adequately funded?
Dr. Penn. There are always things that this institute could
do with more funding. We are delighted at what we have been
getting, and I do not think we could say anything else.
Senator Specter. Well, what would you like to do if you had
more funds?
Dr. Penn. If we had more funding, we could stretch it
further. We have a tremendous base of people that we are
funding now, so we have committed to those folks, and when you
subtract that even from the increases, you are somewhat
surprised that it is not perhaps stretching quite as far as we
want. We have major, major disorders, as you know, that we have
to cover.
Senator Specter. What prospects are there, if any, for
curing muscular dystrophy?
Dr. Penn. I personally think that there are excellent
prospects, because the energy is so high and the possibilities
are so great, and I tried to outline them, and I think you will
hear more from Dr. Sweeney.
However, it was never easy. If it had been easy, it would
have been done a lot sooner than this, and I think a lot has
happened. A lot has happened in terms of the viruses, both a
lot of good as well as some bad. We have a major hurdle which
involves immune responses both to any vectors used and to the
protein. If you have never had this protein from the beginning
because your gene is missing, then an immune response will
occur, so that has turned out to be a deleterious effect, even
in the mouse.
Senator Specter. What assistance would you think possible
in the long run, by the use of stem cell research?
Dr. Penn. We think that stem cell research, and in
particular a muscle cell, something called the myoblast, which
is always in muscle, including in adult life, could be
extraordinary, because a great deal of work and a great deal of
funding has gone into taking a cell which is further along in
the differentiation path but can make muscle.
Myoblasts do not last very long when they are put in there,
and they do not really disperse through the muscle, so the big
problem is, how are you going to take myoblasts, which you can
isolate and put them in a large muscle like the muscles of your
thigh, and get them all through the thigh.
Senator Specter. But you think stem cells do have
potential----
Dr. Penn. They may be able to do this.
Senator Specter [continuing]. For possibly finding a cure
for muscular dystrophy?
Dr. Penn. And even more, a cell in muscle now, which can be
isolated and actually cause to differentiate further, something
called the satellite cell. That cell is a certain form of stem
cell. What is so interesting is that it is similar in ways to
cells in the blood, and, as we know, the bone marrow has stem
cells. That kind of stem cell is already there.
Senator Specter. The lights have not been working, but I
think my 5 minutes has expired, so I will turn to Senator
Wellstone.
Statement of Senator Paul Wellstone
Senator Wellstone. First of all, Dr. Penn and all that are
here, I thank Senator Specter for his graciousness. I am
actually not a member of this Appropriations Committee, but I
am very, very committed to everybody that is here and to the
work that you do, Dr. Penn.
I will just follow up very quickly on two questions that
the chairman asked you, one on the overall question of budget
and what would you do in the best of all worlds. Sometimes I
see you when we are talking about Parkinson's and other
neurological diseases. Today it is muscular dystrophy, and I
have been working with the people in Minnesota on Duchenne's
disease, and it seems to me that the one thing I think all of
us hope and pray for, more than anything else, is that we have
the kind of budget where we do not have one group of people who
are struggling with an illness played off against another group
of people. I mean, that is not what this is about.
So I think it is very, very important, and I appreciate
your work, Mr. Chairman, in really bumping up the
appropriations. Sometimes when we talk about some diseases,
there may not be that large a number of citizens affected. Take
Duchenne's disease. Children are affected, and whatever the
numbers, for the families this disease is the most important
thing of all. Today we are focusing on muscular dystrophy
including Duchenne's, and I want to tell everybody here, that
you are the most powerful citizen lobby imagined. I mean, if
you are not here, and you are not speaking for yourselves with
loved ones, it just will not happen, and I thank you.
So I think we really ought to work on the budget, and then
on stem cell research. I know this is a very controversial
question, but boy, I just have to say, Mr. Chairman, I was
listening to a report on National Public Radio this morning
about the debate, and I think that done the right way, with all
the safeguards that there is no question that stem cell
research must be allowed to continue. It would be so tragic if
we cannot go forward with this research, which has such promise
in terms of finding cures for terrible diseases and helping so
many people and so many families.
So we are really at a very, very critical point when it
comes to the research and what we need to do as a Nation. I
consider this to be an historic hearing, so I thank you, and I
look forward to listening and when I do leave it is not for
lack of interest, it is because I have another commitment, but
I wanted to be here and I thank you for allowing me to be here.
Senator Specter. Thank you very much, Senator Wellstone.
Thank you very much, Dr. Penn.
Dr. Penn. Thank you, sir.
STATEMENT OF LEE SWEENEY, Ph.D., SCIENTIFIC DIRECTOR,
PARENT PROJECT MUSCULAR DYSTROPHY
Senator Specter. I would like to turn now to the second
panel, Dr. Lee Sweeney and Dr. Leon Charash.
Dr. Sweeney is chairman of the physiology department of the
University of Pennsylvania School of Medicine, and serves as a
professor of medicine and surgery. He is the scientific
director for the Parent Project Muscular Dystrophy, and directs
the neuromuscular disease program at the Institute for Human
Gene Therapy. He has a bachelor's in biochemistry from MIT, and
Ph.D. in physiology and biophysics from Harvard University.
Thank you for joining us, Dr. Sweeney, and we look forward to
your testimony.
Dr. Sweeney. Thank you, Senator, and I greatly appreciate
your invitation to testify today, and especially to be allowed
to represent the muscular dystrophy community.
Dr. Penn made a number of points that I wanted to make, and
they are reiterated in my written testimony so I will not go
through them again, but I would say that her point about there
being multiple forms of muscular dystrophies that have
different ages of onset and different severities of the
diseases is a point worth remembering, and the fact that we
have very little insight into some of these diseases, such as
FSH and other diseases. We know a lot about what causes them,
but the commonality there is we can do very little to treat any
of these diseases.
When most people think of muscular dystrophy they think of
Duchenne muscular dystrophy. It is hard not to remember the
images of the young boys afflicted with this disease. It
afflicts one out of every 3,500 newborn boys throughout the
world, and it arises spontaneously in about a third of the
cases, that is, no family history of the disease prior to the
newborn child.
As I said, and as Dr. Penn said, work that was sponsored by
the NIH and by the Muscular Dystrophy Association led to the
discovery of the dystrophin gene in 1987, and yet since then
there has been really very little done to change the way we
treat these boys, and very little Federal research has actually
gone into developing new treatment options.
An increased commitment is needed on the part of NIH to
focus on basic muscle biology research, muscular dystrophy
research, and DMD in particular, in order to drive new
initiatives and drive new discovery. Admittedly, Congress has
been very generous to NIH. However, research on the muscular
dystrophies has not proportionally benefited from your attempts
to double the NIH budget.
I think in large part it is because muscle biology and
muscle diseases research was historically an underfunded field.
The entities primarily responsible for funding them were not
funding to the highest levels within NIH. This has been
compounded, certainly in recent years, by in my opinion what is
an inadequate review process for muscle disease grants in
place, for muscular dystrophy grants in particular, and so even
though more money is available, it is not really benefiting
these diseases to the extent that it should be.
It is not due to a lack of opportunity in basic and disease
treatment research--I gave several examples, parenthetically
all from your home State--but these include viral gene therapy,
drug-based therapies, even stem cell therapies, so there are a
lot of opportunities there, and we are getting to the point
where you can probably cure a mouse, but we are a long way from
actually treating a boy or an adult with any of these muscular
dystrophies.
Now, last year, Congress passed the Children's Health Act
of 2000, which included language that increased the
coordination among the appropriate Institutes at NIH to
maximize resources in efforts specific to muscular dystrophy
research. This has had a major effect, and the NIH, in
particular the NINDS and NIAMS, have made significant progress
in working with the research community, exploring new ways to
encourage researchers to focus on these diseases. You heard
about the workshops that Dr. Penn spoke of. H.R. 717 is another
attempt, directed in this case at DMD in particular, to move
forward.
So again, I commend Chairman Specter and the committee for
their support of NIH, their commitment to double its budget,
and I believe it will have a great impact on the muscular
dystrophy community. We are on the verge of making meaningful
progress in the treatment of these diseases for the first time
in history, but we cannot do it without the Federal Government
continuing to express its interest and really pressing NIH to
focus on these diseases.
PREPARED STATEMENT
So as you begin your appropriations process, I encourage
you to consider the lives of the people afflicted with these
diseases, and the lives of their families. Especially consider
that these are equal opportunity diseases. They cross all
racial, ethnic, and socioeconomic barriers. They can arise in
any family, even your own.
Thanks for your compassion, and I would be happy to answer
any questions.
[The statement follows:]
Prepared Statement of Lee Sweeney
My name is Dr. Lee Sweeney, and I am the William Maul Measey
Professor and Chairman of the Physiology Department at the University
of Pennsylvania School of Medicine. Today, I am testifying at the
request of the Parent Project MD, as an expert in muscle biology,
regarding muscular dystrophy in general, but with a focus on Duchenne
muscular dystrophy, and its weaker form, Becker muscular dystrophy. I
appreciate the invitation to testify today and I want to especially
thank Senator Specter and Senator Harkin for allowing me the
opportunity to speak on behalf of the muscular dystrophy community.
There are five key points that I would like to make in my testimony
today:
(1) There are many forms of muscular dystrophy, many of which are
poorly understood, and for most of which we have made no progress in
treatment of the disease;
(2) Duchenne Muscular Dystrophy (DMD) is the most common lethal
childhood genetic disorder, affecting one in every 3,500 newborn boys
worldwide;
(3) Although the dystrophin gene that is defective in DMD was
successfully identified by medical researchers in 1987, federal
research devoted to potential treatment options has been minimal;
(4) Increased federal commitment to medical research for basic
muscle biology, muscular dystrophy in general, and DMD in particular,
is critical for supporting promising new research initiatives and to
drive new discovery;
(5) While Congress has been generous to NIH, research on muscular
dystrophies needs special attention to attract new investigators into a
historically under-funded area.
Muscular dystrophy is a broad term that refers to a number of
primary diseases of muscle. These include dystrophinopathies (Duchenne
and Becker), myotonic dystrophy, distal myopathies, Emery-Dreifuss,
facioscapulohumeral, oculopharyngeal, and the limb girdle muscular
dystrophies. Many aspects of these diseases are not understood, and
treatments are either unavailable or minimally effective. The age of
onset and severity of these diseases is highly variable.
Mention muscular dystrophy and Duchenne muscular dystrophy (DMD) is
the one that most people think of, whether or not they know its name.
Images of its victims, the young boys, don't easily leave your mind.
DMD is the most severe of all of the muscular dystrophies. It is the
world's most common and catastrophic form of genetic childhood disease.
DMD represents 90 percent of all childhood onset muscular dystrophy
cases, and is characterized by rapidly progressive muscle weakness that
results in death, generally by 20 years of age. One in 3,500 male
children will be born with the disease, about a third of them into
families with no previous history of the disease. These boys will lose
the ability to walk by age 10, and will gradually lose their ability to
breathe, until they die in their late teens or early twenties.
Although we have known the gene (dystrophin) that is affected in
DMD and Becker muscular dystrophy since 1987, no significant treatment
that extends the lifespan of DMD children has been developed. The only
drugs that are known to provide any benefit are steroids, which have
serious side effects in the children. Less than 1/1000 of the NIH
budget is focused on research linked to muscular dystrophy. Of the
$17.8 billion budget for NIH in fiscal year 2000, only $9.2 million was
invested in medical research specific to DMD. Because of the limited
federal support for medical research specific to various forms of
muscular dystrophy, current treatment options are minimal in efficacy,
and are aimed at simply managing the symptoms in an effort to optimize
quality of life, without impacting lifespan.
This is not due to a lack of opportunities in basic and disease-
treatment research. There are significant advances being made that
could someday be translated into treatments that would drastically
change the progression of the disease. For example, researchers at the
University of Pittsburgh have recently engineered a possible gene
therapy for DMD. They were able to fit the critical elements of the
dystrophin gene into what currently appears to be the safest and most
promising viral vector for the treatment of muscle disease. Their work
demonstrated that a small piece of dystrophin could be delivered to
muscle when placed into adeno-associated virus (AAV). The virus causes
the muscle to begin making the piece of dystrophin, which may be
sufficient to stop the progression of the disease. In mice, the
dystrophin expression has continued for more than one year, and likely
will go on much longer.
My own lab at the University of Pennsylvania has used AAV to
produce a growth factor in muscle (IGF-I) that we think can be used to
treat many forms of muscular dystrophy, as well as stop the loss of
muscle in all of us as we get old. Our tests in old and dystrophic mice
have been dramatic, in that muscle function has been preserved
throughout life by the over-expression of this growth factor in muscle.
My lab also recently demonstrated that a common antibiotic might be
used to treat a small percentage of DMD patients, again based on
successful studies in mice.
These are but a few examples (all from Senator Specter's home
state) of many that I could provide. Yet there should be many more and
there should be more rapid progress in bringing these treatments from
mouse to man. Although Congress has been extremely generous with NIH,
proportionately little of the increase has benefited the muscular
dystrophies. This is in part because of the reticence of new and
established investigators to enter a historically under-funded area;
namely, muscle biology and muscular dystrophy. Until the last few years
(and only then likely due to Congressional interest) NIH has put little
emphasis on the muscular dystrophies. Scientists will not enter a
research area unless they perceive that funding is available for
research. Furthermore, in my opinion there have been significant
problems in the manner in which grants that deal with muscle disease
have been reviewed, resulting in too few being funded. Attention is now
being given to this problem, again because Congress has expressed its
concern. Last year the Congress passed the Children's Health Act of
2000, which included a title that increased coordination among the
appropriate Institutes at the NIH in order to maximize resources and
efforts specific to muscular dystrophy research. The NIH, and in
particular the National Institute for Neurological Disorders and Stroke
and the National Institute for Arthritis and Musculo-Skeletal Disease,
have made significant progress in working with the scientific research
community on exploring new ways to encourage researchers to focus on
all aspects of the muscular dystrophies. The support of these
Institutes has been invaluable, and our hope is that they will continue
to support the muscle research community in its endeavor. We also hope
that the Center for Scientific Review within NIH will become more
responsive to the inadequacies in the review of muscle research.
A recent Congressional initiative that could further benefit DMD
research is the recent introduction of H.R. 717, the DMD Childhood
Assistance, Research and Education Act (also referred to as the DMD
CARE Act). Due to the advocacy efforts of the Parent Project MD and the
leadership of Representatives Roger Wicker and Collin Peterson who co-
introduced the bill, H.R. 717 now has over 100 co-sponsors. This
important legislation would establish an MD interagency committee
within the NIH in order to expand opportunities for collaboration.
Additionally, the bill calls for the creation of three Centers of
Excellence through NIH and CDC so that leading research institutions
will have an opportunity to compete for federal support towards both
epidemiological and clinical research.
Again, I commend Chairman Specter and the Committee for their
support of NIH and their commitment to doubling the NIH budget. I
believe that this will have a great impact on the muscular dystrophy
community. A mere increase of $20 million a year directed at muscular
dystrophy research could transform our treatment and understanding of
these diseases. We are on the verge of making meaningful progress in
the treatment of DMD for the first time in history, but we cannot do it
without support from the federal government.
While all of the muscular dystrophies have significant impact on
the quality of life of the affected individual, the childhood muscular
dystrophies, and DMD in particular, have tremendous repercussions for
the family members and caregivers. Currently there exists only a small
quantity of public information about DMD and other childhood muscular
dystrophies, and what little information does exist remains
inadequately disseminated and insufficient in addressing the needs of
specific populations and other under-served groups. Many family
physicians and health care professionals lack the knowledge and
resources to detect and properly diagnose the disease at an early
state, thus exacerbating the progressiveness of the symptoms that go
undetected or misdiagnosed. Educating the public and the health care
community throughout the country is of paramount importance, and is in
the public interest and will benefit all communities.
Today's hearing is a major step towards creating a greater public
awareness of muscle disease, and I'd like to personally thank the
Members of the Committee and their staff for showing their interest in
the DMD and other muscular dystrophy communities. As you begin this
year's appropriations process, I encourage you to consider the lives of
those affected by these diseases. Especially consider the lives of your
own sons and grandsons when thinking about DMD, as it is a disease that
knows no boundaries.
Thank you for your time and compassion. I would be happy to answer
any questions.
Senator Specter. Dr. Sweeney, the subcommittee and the full
Congress is very concerned about the lives of the people who
are affected here, and you have accurately characterized it as
generous by any standards, but you are really making a fairly
severe indictment, as I listen to you, that NIH is not doing
the job. Do I hear you wrongly?
Dr. Sweeney. I would not say not doing the job. I think the
problem is----
Senator Specter. Well, they are not pursuing avenues to get
the maximum use for the money to solve the problem.
Dr. Sweeney. Well, I think the problem is that when an area
lies fallow for too long and scientists do not go into it, then
just making money available across the board does not do
anything.
Senator Specter. Well, has it lain fallow? There have been
very substantial appropriations for the Institutes, always, and
you heard the particularization of the increases of about 16
percent, and $1.4 billion. That is a very substantial sum of
money.
Dr. Sweeney. Yes, the overall budget is certainly very
generous, and it is just, I think in this case something needs
to be done, as the Institutes have started doing in the last
year, to encourage investigators to move into this area, to
highlight that there are research opportunities.
Senator Specter. Well, have they encouraged investigators
to move into this area only in the last year? If so, that is a
strong indictment, Dr. Sweeney.
Dr. Sweeney. Well, I would say that the only significant
efforts have really been within the last year or so, although I
cannot characterize going back much more than 10 years, because
then you go back beyond my career.
Senator Specter. Well, that leaves 9 years for analysis.
Dr. Sweeney. Yes.
Senator Specter. I would like to ask staff to meet with
you, Dr. Sweeney, and get the particulars, because if you are
right, some changes need to be made.
Please note that I said, if he is right.
Dr. Penn, why don't you come forward and make a response
here. What do you think? Is Dr. Sweeney even partly right?
Dr. Penn. I think, Senator, that more people, more really
good investigators, as I sort of indicated, could definitely be
working in this problem, and I think some things have now come
forth where we need those people. We need people that know
about these viruses. We need----
Senator Specter. Well, don't you have good investigators
working on it now?
Dr. Penn. We do now, but remember, the revolution in
molecular genetics is really not that old either, so----
Senator Specter. You are talking about identifying the gene
in 1987.
Dr. Penn. Yes, but identifying the gene, as I said,
produced information which nobody was ready to really take care
of, because it is so big. I mean, we did not know exactly--we
still do not know precisely what that protein does.
I will not say that more could not have been done in this
disorder by NIH over time to take advantage of all the new
information coming out, and making sure that all that new
information was applied to the dystrophies. I think that the
workshop helped. We certainly knew who was out there working.
We always say that we need more good scientists in all of
our particular disorders, and I do not want to say that any of
the institutes at NIH that are working on this disorder have
not contributed to what has happened. I understand the issues
about review. We will have a big meeting in the middle of
March, which I am sure Dr. Sweeney will attend, to talk more
with our Center for Scientific Review about how to review these
applications. If people do not get funded, they get
discouraged.
Senator Specter. Well, Dr. Penn, your comments are just too
high a level of generalization.
Dr. Penn. Yes, sir.
Senator Specter. More could be done, and you would not say
that some progress has not been made. You have been very
handsomely funded.
Dr. Penn. Yes, sir.
Senator Specter. And for that money the Congress expects
results, and I would like you to sit down with Dr. Sweeney and
staffers and get down to brass tacks as to what his complaints
are and what your responses are.
Dr. Penn. I would be pleased to do that, sir, and I think
we know a lot about what Dr. Sweeney has in mind.
STATEMENT OF LEON CHARASH, M.D., CHAIRMAN, MEDICAL
ADVISORY COMMITTEE, MUSCULAR DYSTROPHY
ASSOCIATION
Senator Specter. Dr. Charash, thank you for joining us,
chairman of the Medical Advisory Committee and spokesman for
the Muscular Dystrophy Association. Since the 1980's, Dr.
Charash has provided a guiding hand on research programs,
continues his private practice, is associate clinical professor
of pediatrics at Cornell, M.D. from Cornell, specializing in
pediatric neurology.
Thank you for joining us, Dr. Charash, and the floor is
yours.
Dr. Charash. Mr. Chairman, Senator Craig, and Senator
Wellstone, I have some exceptions to some of the things that
have been stated here.
There was a question made about whether we have been
suboptimal in treating patients. The Muscular Dystrophy
Association, founded in 1950, has expended over $1 billion to
treat patients. We have a clinic in every major medical school
in the United States, one in Children's Hospital here in
Washington, where free care is given to anyone who needs
diagnostic and therapeutic services.
The Muscular Dystrophy Association, incidentally, was
founded by a group of parents in 1950, and with Jerry Lewis'
leadership has expanded to the point where it has a worldwide
program sponsoring research around the world.
The critical question you asked, Senator, was, is there
anything we would like to do? There is something we must do,
because we have been successful. In these 50 years of research
since MDA was founded, all the knowledge of muscle disease
would fit into three paragraphs in Cecil's Textbook of
Medicine. Now there are volumes on it. We have learned
everything we wanted to know about muscle biology, histology,
physiology, chemistry, and we have also now found the gene for
every single disorder, essentially, that produces muscular
dystrophy.
And by the way, we did find the gene, Senator, in 1957, and
2 years later we convened the first world conference of what is
called myoblast therapy, and a year after that we treated the
first human being with myoblasts, which are stem cells, and we
expanded that to other clinics, and then we have used viral
vectors. What we have gotten out of, though, is not something
we should do, it is something we must do, because we built up a
platform of information. All of this knowledge, in 50 years,
has swelled the platform to where we can now shoot a rocket up.
We have never been able to translate all of this knowledge into
effective treatments.
We have strategies, and Dr. Penn very eloquently described
antibiotics, stem cells derived from muscle or bone marrow,
viral vectors to do this. MDA started it, initiated the first
and only human trial to give a gene to muscular dystrophy
patients, a virus, to a gentleman seated over here. Where is
he? Over there. I was present in Columbus, Ohio, when he got
his first injection. It is the only trial ever done.
We have to plan. We have to be proactive. We got all the
information. We have not done anything about it, but we have
not had that very long. We just got it now. The iron is hot. We
have to strike. To do that, we have to have a focused program
to translate all that we know into treating muscle diseases,
and I might suggest this. If we can treat muscle disease, we
can treat all genetic disease, and muscle is the best tissue to
use.
Diabetes is a disease of the pancreas with islet cells.
Muscle is the biggest tissue in the body. Muscle is accessible.
We can see it. We can see if it has atrophied. We can see what
its tone is like. We can biopsy it. We can do electrical
studies on it.
If we can find a way to crack open genetic treatment of
muscular dystrophy with stem cells, or with viral vectors, or
whatever else, the door will be open. If you are watching the
progress of treating diabetes, to take a needle biopsy of the
pancreas is invasive and dangerous. We can take needle biopsies
of muscles as often as we want, safely.
PREPARED STATEMENT
So I think the Muscular Dystrophy Association, which has
devoted itself to all the dystrophies for 50 years, is
passionately interested in seeing the NIH not only increase its
funding, but set up a protocol where there can be a research
body, and set up institutions, satellite institutions and help
break down all genetic diseases.
Thanks.
[The statement follows:]
Prepared Statement of Leon Charash
Thank you Mr. Chairman, Senator Harkin and members of the
Subcommittee for this opportunity to address you. I'm here today to
call your attention to a matter of life and death for tens of thousands
of children and adults affected by muscular dystrophy. Muscular
dystrophy is the name given to a group of disorders caused by genetic
defects and characterized by weakening and eventual wasting of
voluntary muscles. The muscular dystrophies can weaken the muscles of
the heart and those required for breathing. By profession, I'm a
pediatric neurologist and I've treated many children with muscular
dystrophy.
In 1950, a group of parents and other relatives of muscular
dystrophy patients, concerned that virtually nothing was being done to
combat these diseases, organized to form what is now the Muscular
Dystrophy Association. For over 50 years, the Association has provided
help through medical services and hope through research for youngsters
and adults with any of the nine forms of muscular dystrophy. And it's
thanks to hundreds of millions of dollars in research funded by MDA
that tremendous developments in understanding the causes of these
disorders have occurred. Today, virtually all of the genetic defects
that cause the muscular dystrophies are known.
The obvious next step is the development of effective therapies. A
number of strategies are being pursued to correct the gene defects in
the muscular dystrophies. Some are in the early stage of development
and have shown encouraging results. Others are in the clinical trial
phase. One approach now in clinical trials involves the use of
antibiotics. MDA-funded studies of how cells make proteins led to the
discovery that some antibiotics can override a ``stop'' message in
genes that make the critical muscle protein dystrophin. Also, therapies
using resident stem cells have shown encouraging results in early
studies and, based on those results, will eventually be applied in
clinical trials. Another strategy is gene therapy designed to replace
missing or defective muscle proteins.
Scientists are optimistic about the therapeutic potential of these
new techniques. However, the price tag is high. MDA funded and
initiated the first gene therapy clinical trial in a muscle disease in
September 1999. The project was a phase-one trial in which only six
individuals were slated to receive gene therapy. The budget for this
initial trial alone was nearly $5 million. It's clear that continuation
and expansion of these studies depends upon an increased financial
commitment. For the first time in the history of these terrible
diseases, we are not limited by science.
While MDA will not only continue to press ahead but will increase
its efforts in search of treatments and cures, we believe strongly that
a major investment through the National Institutes of Health will be
essential to advance to the next level in muscular dystrophy research.
To this end, we propose that the projected $19.9 million NIH annual
commitment for muscular dystrophy research be increased by $100
million. We also propose that an NIH study group be established for
neuromuscular disease research.
An analysis of NIH expenditures on diseases that affect a number of
people similar to that affected by muscular dystrophy shows a great
disparity in spending. In fact, spending on some of these disorders,
and even on some that affect far fewer people, is many times the amount
allocated for muscular dystrophy research. We seek this Subcommittee's
support in our effort to meet the challenge of taking muscular
dystrophy research to the next level--the development of effective
treatments for 250,000 American children and adults.
Thank you.
Senator Specter. Thanks very much, Dr. Charash.
Senator Craig.
Statement of Senator Larry Craig
Senator Craig. Mr. Chairman, on this issue my learning
curve is about like this, and I am pleased that you are holding
this hearing, because it is tremendously important that we
cause our institutions to focus.
This Congress has been committed now for several years to
advancing increasingly large sums of money to go directly at
and to pay for the quality of research and bring folks online
who are dedicated to these areas, and these kinds of hearings,
as I think Senator Wellstone said, help us focus, and they help
the institutions of our Government that are dedicated to these
kinds of efforts focus along with us.
I will continue, as certainly this committee has, to
support increased funding. We now are fortunate enough to have
the resources to attack in ways that we have not in the past,
and we also have the knowledge and the technologies to do so,
so thank you all for being here this morning to help us.
Senator Specter. Senator Wellstone.
Senator Wellstone. Maybe I will try to build on, Mr.
Chairman, a question or really a comment on your part to Dr.
Sweeney.
Dr. Sweeney, you had talked about DMD, and until I met
Cheri Gunvalson from Minnesota who is here today, I just really
had so little knowledge of this terrible disease. Part of the
problem it seems to me has been the invisibility of muscular
dystrophy, at least as it affects children, especially with
Duchennes, and that there has been such a small number of
families that have been affected in the whole country that
there just has not been the presence and the clout, or the
focus to get the research that is needed, or is it something
else going on here?
Dr. Sweeney. I think it is a number of factors, and I think
there is good visibility. I mean, the MDA has for a number of
years raised the visibility of the muscular dystrophies in this
country. I really think that the problem I perceive, and I
guess we can debate whether there is a problem, within NIH is
really not a lack of interest on the part of the institutes,
but it is more----
Senator Wellstone. No, I do not think there is a lack of
interest.
Dr. Sweeney. It is more of a problem, as I said, in sort of
the way these grants get reviewed. I mean, the vagaries of the
review process at NIH in large part dictate what sort of work
gets funded. Study sections get set up that focus on a certain
area. There is not a good home to review grants that deal with
the muscular dystrophies, and because of this I think they are
chronically underfunded, and because of that, new investigators
are discouraged from going in to the area.
This was brought home--I went to a workshop that NIAMS held
a few weeks ago, a very small one, where we were talking about
better diagnostics that could be used in the skeletal muscular
dystrophies, and all the technology that we were talking about
had originally been developed in skeletal muscle now is being
used in the heart. When the experts were asked, well, why isn't
it being used in skeletal muscle, for those diseases, they
said, well, there was no funding, and so we went to work on
heart.
So I mean, it is a perception in the community, and you
know, where there is a perception, it needs to be addressed.
Senator Wellstone. Let me ask you this, and Dr. Charash can
also respond. Senator Specter said he would like to get a
number of you all together to sit down and deal with concerns
and answers, and I do not assume anything but good faith on the
part of NIH, but what would you recommend for muscular
dystrophy, and in particular for DMD? I guess my question is:
What would you say specifically we need to do?
Dr. Charash. We have been working on Duchenne. It is a big
gene. We cut it down to a smaller size, which works. We have
taken the virus and stretched it as a vector. We have used it
in animals. We cannot separate Duchenne research from all the
other dystrophies, for this critical reason. We cannot treat a
child without informed consent. We do not believe it is moral
or ethical to have a--or even to ask a parent to sign--now,
we----
Senator Wellstone. You do not have to separate out what
would be the priorities for overall research? What would you
change right now?
Dr. Charash. A task force funded by the NIH, translate all
that we now know about--we have identified the genes. We know
ways in which we can enter it into the body, and the stem cells
that can be harvested from adults, and we need a task force--
incidentally, I think Jerry Lewis is going to make a request to
this committee for what he thinks should be done, and that is
the view of MDA.
Senator Wellstone. Dr. Sweeney.
Dr. Sweeney. I think a couple of things could be done. I
think whenever you have got an area that needs a jump start,
like this one now needs to reinvigorate it, I think some
initial targeted funding for the area is justifiable, but I
think moreover, the long-term solution comes in addressing the
review process and to create a study section that can
deliberate on disease, muscle disease-related grants and muscle
biology in general. I mean, this is true for cardiac issues. It
should be true for skeletal issues.
And then centers to bring about more rapid translation of
research, such as has been suggested in the case of DMD and
H.R. 717, that would set up translational centers that could
take the basic biology and the preclinical data and begin to
move it.
So I think, you know, in the long term it is not about
giving more money to NIH. It is about directing some money in
the short term and fixing the review process for the long term.
Senator Specter. Thank you, Senator Wellstone.
Dr. Charash, you commented about, I mean, now I have all
the information, it is time for action plan, a task force. We
did not just get all the information this morning. How long
have we had it?
Dr. Charash. Well, you know, we have explored a number of--
we started the first human trial, but for safety alone, and we
chose adults, and if it works in adults----
Senator Specter. Dr. Charash, the point I am making is, why
have we languished? How long have we had the information which
would warrant an action plan, and have not done it?
Dr. Charash. Well, we have had it for 1\1/2\ years, and we
have started on the first--it has cost us $5 million just for
the first trial on safety alone. If we're going to expand that
to efficacy, it is going to be a fortune, and it overwhelms----
Senator Specter. Do you know how many $5 million there are
in $1.4 billion?
We have another panel to hear from, but the subcommittee is
going to pursue this to find out what the answer is, and we
would appreciate, Dr. Charash, if you would join Dr. Sweeney
and Dr. Penn in telling us what we need to do to get some
concrete results.
It is a very difficult matter for Congress to instruct the
scientists. Saying it is difficult is an understatement. It is
an impossible matter for the Congress to instruct the
scientists, but other scientists can instruct the scientists.
Independent scientists can come in and take a look at it, and
that is what we would appreciate it if you would do.
Okay. Thank you very much, Dr. Charash, Dr. Sweeney, Dr.
Penn.
Dr. Sweeney. Thank you, Senator.
Senator Specter. We now turn to panel three, Mr. Donavon
Decker, Mr. Chris Rosa, Ms. Patricia Furlong, Mr. Benjamin
Cumbo, and last but not least, Mr. Jerry Lewis.
We are going to have Mr. Lewis serve as clean-up hitter
here, and we are going to start with Mr. Donavon Decker, an air
traffic control specialist for the Federal Aviation
Administration with the Huron automated light service station
in Huron, South Dakota. He was diagnosed with limb girdle
muscular dystrophy at the age of 15. He has four sisters and
two nieces who have muscular dystrophy. In 1999, Mr. Decker was
the first patient to undergo gene therapy for muscular
dystrophy. He has participated in the past seven muscular
dystrophy telethons.
STATEMENT OF DONAVON DECKER, LIMB-GIRDLE MUSCULAR
DYSTROPHY PATIENT, HURON, SOUTH DAKOTA
Senator Specter. Mr. Decker, we welcome you here, and look
forward to your testimony, and when it is convenient for you we
would like to know what the gene therapy was that you
undertook.
Mr. Decker. Thank you, Mr. Chairman. I will start off by
reading my testimony and then follow up with any questions.
Thank you, Mr. Chairman and members of the subcommittee for
permitting me to speak to you today. My name is Donavon Decker
from Huron, South Dakota. I am employed at the Huron Automated
Flight Service Station as an air traffic control specialist for
the Federal Aviation Administration.
I am 38 years old, and have a form of muscular dystrophy
that affects arms, shoulders, legs, and hips. It is called
limb-girdle muscular dystrophy. Limb-girdle muscular dystrophy
is a genetic disorder. My family is a classic example of how
the disease can affect many members of the same family while
skipping a generation. There are 8 children in the family, and
I have 19 nephews and nieces. Four of my sisters and two of my
nieces have limb-girdle muscular dystrophy. Neither my mother
nor my father had any symptoms of the disorder.
In 1999, as you stated, I had the opportunity to become
part of a milestone in research, the first-ever gene therapy
clinical trial for muscular dystrophy. The Muscular Dystrophy
Association funded the trial, which cost approximately $5
million.
As part of the historic project, I was the first person in
the trial to receive injection of billions of new genes. One
foot muscle was injected with new genes and the other received
a sham injection. This is a phase 1 safety clinical trial, and
was a collaboration among researchers representing three
universities, the Ohio State University, University of
Pennsylvania, and the University of Iowa. The test results will
be done in a month or so.
This research has the capacity to be used on all types of
dystrophies, therefore helping individuals from young children
to adults. I believe this trial would have not taken place if
it were not for the Muscular Dystrophy Association. I would
like to recognize the person who has served as the national
chairman of the MDA for over 50 years, Mr. Jerry Lewis, and I
am certain that you all know Jerry for his dedication each
Labor Day you are aware of when he hosts his telethon for the
association.
In the United States, some 250,000 people have one form of
the nine muscular dystrophies, which affects all children as
well as adults, regardless of race, creed, or color. Last year,
the Federal Government budgeted $19.9 million for muscular
dystrophy research. I must say this is very disappointing to
myself and my family. I am certain that many other families
living with muscular dystrophy share my disappointment. But
this can change. We can only win the battle much quicker with
your help. The support of your subcommittee could make a
positive difference in the lives of young people and adults
with muscular dystrophy. It can make a difference in my life.
I urge this committee's consideration of support of a
substantial increase for the allocation of funds for muscular
dystrophy research. The Muscular Dystrophy Association is doing
its job. I am now asking for additional support from NIH-funded
researchers.
When I am at home, I do not use a wheelchair. However, when
I travel I do, because it is easier on myself and the people
that travel with me. I can no longer walk very far, and I
cannot walk inclines without stairs or a wall to lean on. Three
of my sisters use a wheelchair for daily activities.
PREPARED STATEMENT
I know that in a couple of years, if nothing is done I will
be confined to a wheelchair for the rest of my life. The lives
of others will be cut far too short if a cure is not found.
Together, we can make this work so it will not happen. We need
to do whatever it takes to keep this from happening. I and
thousands of others affected by muscular dystrophy are counting
on you.
I would answer any of your questions at this time.
[The statement follows:]
Prepared Statement of Donavon Decker
Thank you Mr. Chairman, Senator Harkin, and members of the
Subcommittee for permitting me to speak to you today. My name is
Donavon Decker from Huron, South Dakota. I am employed at the Huron
Automated Flight Service Station in Huron as an Air Traffic Control
Specialist for the Federal Aviation Administration.
I am 38 years old and have a form of Muscular Dystrophy that
affects the arms, shoulders, legs and hips. It is called Limb-Girdle
Muscular Dystrophy. Limb-Girdle Muscular Dystrophy is a genetic
disorder. My family is a classic example of how the disease can affect
many members of the same family while skipping a generation. There are
eight children in my family and 19 nephews and nieces. Four of my
sisters and two of my nieces have limb-girdle muscular dystrophy.
Neither my mother nor my father had any symptoms of the disorder. My
mother is still living while my father was killed in a construction
accident in 1987.
In 1999, I had the opportunity to be a part of a milestone in
research the first ever gene therapy clinical trial for muscular
dystrophy. The Muscular Dystrophy Association funded the trial, which
cost approximately $5 million. As part of the historic project, I was
the first person in the trial to receive an injection of billions of
new genes. One foot muscle was injected with new genes and the other
received a sham injection. This phase I clinical trial was a
collaboration among researchers representing three Universities: Ohio
State University, University of Pennsylvania and the University of
Iowa. For the researchers to properly monitor my progress, I had to
have muscles taken from both feet six weeks after the injections. The
test results will be done within a month or so.
This research has the capacity to be used on all types of
dystrophy's, therefore helping individuals from young children to
adults. I believe this trial would not have taken place if it weren't
for the Muscular Dystrophy Association. I would like to recognize the
person who has served as the National Chairman of the MDA for over 50
years, Mr. Jerry Lewis. I am certain that you all know Jerry for his
dedicated efforts each Labor Day Weekend when he hosts his Telethon for
the Association.
I want to thank Jerry for making it possible for me to participate
in research that may lead to a treatment for limb-girdle muscular
dystrophy. I want to say thanks to the millions of people who volunteer
countless hours of their time to help MDA. I can't say enough about all
the doctors and researchers funded by the MDA and the magnificent
things they are doing to combat muscular dystrophy. But most of all, I
want to say thank you to the generous public for their support in terms
of dollars to help MDA. The Association has done a great job in putting
those dollars to the best possible use. Again, Jerry, ``Thank You''.
In the United States some 250,000 people have one or another of the
nine forms of muscular dystrophy, which affects children as well as
adults regardless of race, creed or color. Last year, the Federal
Government budgeted $19.9 million for muscular dystrophy research. I
must say this is very disappointing to myself and my family. I am
certain that many other families living with muscular dystrophy share
my disappointment. But this can change. We can only win the battle much
quicker with your help. The support of your subcommittee could make a
positive difference in the lives of young people and adults with
muscular dystrophy. It can make a difference in my life.
I urge this subcommittee's consideration of and support for an
increase in the allocation of funds for muscular dystrophy research in
the amount of $100 million annually to be awarded to researchers by the
National Institutes of Health. The Muscular Dystrophy Association is
doing it's job. Now I am asking for the additional support from NIH
funded researchers.
When I am at home or work I do not use a wheelchair, however when I
travel I do because it's easier on myself and the people that travel
with me. I can no longer walk very far and I cannot walk up inclines or
go up stairs without a wall to lean on. Three of my sisters use a
wheelchair for daily activities. I know that in a couple years if
nothing is done I will be confined to a wheelchair for the rest of my
life. The lives of others will be cut too short if a cure isn't found.
``TOGETHER WE CAN WORK SO THIS WILL NOT HAPPEN''. We need to do
whatever it takes to keep this from happening. I and thousands of
others affected by muscular dystrophy are counting on you.
Senator Specter. Thank you very much, Mr. Decker.
STATEMENT OF PATRICIA FURLONG, PRESIDENT, PARENT
PROJECT MUSCULAR DYSTROPHY
Senator Specter. We turn now to Ms. Patricia Furlong,
president of the Parent Project Muscular Dystrophy, mother of
four children. Two of her daughters are with her today.
Regrettably, both of her sons died of muscular dystrophy. She
is a nurse practitioner and a nurse educator. She served as
Chair for Kids for Kids Project, and we welcome you here, Ms.
Furlong, and look forward to your testimony.
Ms. Furlong. Thank you, Senator Specter. It is an honor to
be here today. Parent Project Muscular Dystrophy would like to
thank you, Senator Specter, Senator Craig, and Senator
Wellstone for being here, and Bettilou Taylor and members of
this committee for this opportunity. We are indeed honored that
voices are heard here in this city and in this place.
I represent the Parent Project Muscular Dystrophy. It is a
nonprofit voluntary health organization comprised of parents
and grandparents whose children are diagnosed with Duchenne and
Becker muscular dystrophy. Our goal was to add in the options
to expedite therapies for Duchenne muscular dystrophy.
Mr. Chairman, today I ask the Members to focus on Duchenne
muscular dystrophy. For years, we have been witness to the
public information that we are almost there, we are around the
corner, answers are on the horizon. Are they? Mr. Chairman, we
are not there. Although there are emerging strategies leading
to therapy and treatment in the future, the NIH investment has
been minimal.
On a sunny day in June 1984, my sons were diagnosed with
Duchenne muscular dystrophy. To this moment, I recall those
words, Mrs. Furlong, your sons have Duchenne muscular
dystrophy. There is no hope and no help. The prognosis is the
same. It has been the same. They may not survive. The physician
then asked me if I had any questions. I wondered why the sun
was shining. I asked him that.
My personal story has to be more than this. It has to be a
collective story about all boys diagnosed with Duchenne and
Becker muscular dystrophy and, following their exposure to
medical intervention, losing all independence. Mr. Chairman,
there is nothing that has changed in 100 years. Nothing will
change without increased investment in Duchenne research.
One day, long ago, my son Patrick was trying to convince me
of a crazy argument he had. He said to me, mom, pretend I am in
a midlife crisis. In fact, he was. He was 8. Duchenne, the most
common lethal genetic disorder of childhood has not had
sufficient attention, and the ordinary person has no
recognition of this disorder, and yet, due to the high
spontaneous mutation rate, every person is at risk.
The clinical explanation does not clearly reflect this
disorder. By the age of 12, most boys have lost their ability
to walk. The child needs help with ordinary things, turning in
bed, lifting a fork, wrapping their arms around someone they
love. By the age of 17, breathing is sometimes difficult.
Often, invasive ventilation is necessary. During the late teens
or early twenties, young men with DMD are unable to manage oral
secretions, and often have to have stool removed because they
are unable to do it themselves. Remember, muscle is not just
for moving bones.
The diagnosis of Duchenne is accompanied by a lifetime of
progressive loss of function, loss of independence, and
dependence on family. It is an extraordinary physical, mental,
psychological, spiritual, and financial burden to the family,
for all of us as a society.
Finally, the loss of these boys. Their absence diminishes
us and the greatness of this country.
Before his death, my son Christopher said to me, if you
will not fight for me, who will? It is for this reason we
started the Parent Project Muscular Dystrophy. Beginning in
1997, the Parent Project Muscular Dystrophy members
successfully initiated a legislative agenda. We began with a
grassroots fundraising campaign. We began meeting with Members
of Congress, Members of the Senate. We began talking about
Duchenne muscular dystrophy here on the Hill.
Last year, we, with your kindness, saw the first title in
the Children's Health Act. This was the first time in history a
Federal mandate for DMD was initiated. This year, on
Valentine's Day, H.R. 717, the DMD Care Act, was introduced in
the House by Representatives Wicker and Peterson, with an
unprecedented 92 cosponsors.
Parent Project Muscular Dystrophy has established extensive
collaborations with the NIH and the Center for Disease Control,
but without adequate funding of these efforts, they will fall
by the wayside, and another generation of children will see no
change in prognosis.
Mr. Chairman, Congress is very generous to NIH, but this
disease, the No. 1 lethal genetic disease of childhood, gets
only 1/1,000ths of the NIH budget. No wonder there is nothing
available for these children.
Our children are not out of their warranty period before
their bodies wear out. They will never receive adult status to
advocate on their own behalf. This generation, this disease
sends ripples of pain and dysfunction through every family. On
behalf of the children with Duchenne and Becker muscular
dystrophy and their families, and all of these people you see
here with muscular dystrophies, we ask the Federal Government
to commit $100 million over 5 years specifically for Duchenne
research. This would change the face of this disease forever
and jump start an important field of research.
PREPARED STATEMENT
Today, we are not seeking exceptional funding for our
children. We seek equity. Respected Members of this Congress,
our battle is against Duchenne and Becker muscular dystrophy.
We seek equity, equity in research opportunities, equity in
set-aside funding, equity in the review process, equity in
worth, the worth of every child with Duchenne and Becker
muscular dystrophy, the worth of every person with muscular
dystrophy.
Mr. Chairman, it is too late for my own sons, but with your
help, this disease will change. Thank you.
[The statement follows:]
Prepared Statement of Patricia Furlong
On behalf of the Parent Project for Muscular Dystrophy Research,
Inc. (otherwise known as the Parent Project MD), I would like to
express the organization's sincere appreciation to Senator Specter,
Bettilou Taylor, and members of this Committee for the opportunity to
testify at today's Congressional hearing.
I represent the Parent Project MD, a nonprofit voluntary health
organization comprised of parents and grandparents whose children have
been diagnosed with Duchenne muscular dystrophy or its milder form,
Becker muscular dystrophy. The Parent Project MD's mission is quite
simple and straightforward: To mobilize people in the USA and Worldwide
in collaborative efforts, enabling people with Duchenne and Becker
Muscular Dystrophy to survive, thrive and fully participate into adult
age. We wish to expedite treatment and a cure for this heartbreaking
muscle disorder by increasing support for research.
Mr. Chairman, today I ask the members to focus upon the most
common, lethal genetic disorder of childhood--Duchenne MD. For years,
we are witnesses to public information that we are ``almost there'' or
``around the corner''. Answers are on the horizon--or are they? Mr.
Chairman, we are not there. Although emerging strategies leading to
treatment and therapy in the future are in the works, NIH investment in
DMD is abysmal, the peer review process and structure is not conducive
to muscle research--simply stated the mechanism to foster science and
research in this is broken. We have to commit adequate resources and
support before the prognosis of DMD will see significant change.
On a sunny June day in 1984, my sons were diagnosed with Duchenne
muscular dystrophy. To this day, I recall the exact words: ``Mrs.
Furlong, your sons have Duchenne muscular dystrophy, you are therefore
a carrier, one or both of your daughters will perhaps be carriers. Your
marriage will fail and your daughters will suffer due to the amount of
care you will necessarily provide for your boys. Do you have any
questions?'' I wondered why the sun was still shining.
THE JUXTAPOSITION OF DUCHENNE
It simply isn't fair to be bright, handsome, and full of potential.
To be well adjusted in a good family, having so much to give the world,
to be so loved and then to die so young. Worse, is to both see and feel
the life force deteriorate slowly, finally and completely--until there
is nothing left. Mr. Chairman, we live in a proactive, positive world,
though children with DMD are ultimately powerless. It just isn't fair
and great injustices must be righted or we are no better than a
``killing field'' through our apathy.
The barriers to progress on this disease says little for us as a
society and as a nation--that due to a lack of significant resources,
clinical outcomes of this disorder are predictable and remain
unchanged. Boys die before reaching 20, before reaching adulthood,
before experiencing life. One day, long ago, my son Patrick was trying
to convince me about one of his crazy ideas and I recall smiling at his
comment ``Mom, pretend I am having a midlife crisis.'' Sadly, age 8 was
midlife for Patrick--his argument was sound.
Duchenne, the most common lethal genetic disorder of childhood, has
not had sufficient attention--and the ordinary person has no
recognition or understanding of this disorder; and yet, due to the high
spontaneous mutation rate, every person is clearly at risk.
My personal story therefore, is a collective story about all the
boys diagnosed with Duchenne, and following his exposure to myriads of
medical intervention, losing all independence and finally his life. Mr.
Chairman, in this, NOTHING has changed in the last 100 years, the story
remains unchanged and will remain so without increased investment in
DMD research. In this remarkable land of medical miracles, we should
all hide our faces in shame on that one statistic; let alone the harsh
reality of this progressive, heartbreaking degenerative process known
as Duchenne.
Duchenne Muscular Dystrophy (DMD) is the most common lethal
childhood genetic disorder in the world, affecting 1:2328 male newborns
worldwide (1997 German study). The disease can be inherited through X-
linked recessive transmission within families, or it may be caused by a
spontaneous mutation in individuals. Children who are born with DMD
follow a predictable clinical course. Young children often develop
difficulty walking and begin falling due to muscle weakness, and by 8-
10 years of age the muscle weakness has progressed to the point where
most children are wheelchair-bound. By their late teens, most DMD
children have succumbed to their disease, usually as victims of
respiratory failure.
This rather clinical explanation does not clearly reflect the
disorder. Children with DMD experience a lifetime of medical
intervention. As toddlers, boys with DMD look quite normal. At
diagnosis--informed physicians refer to baseline studies, night
splints, AFO's and PT--an excessive barrage of medical lingo that will
soon become a second language for the family. As a mechanism to prevent
contractures of the Achilles tendon, hamstrings and ileotibial bands,
gait changes, lordosis, walking on their toes and finally loss of
ambulation, boys with DMD require aggressive physical therapy, ankle-
foot orthosis (AFO's), and long leg braces. By the age of 12, most boys
have lost their ability to walk and, for the rest of their life, will
require an electric wheelchair. In an effort to prevent spinal
curvature, respiratory compromise and bone loss--long leg braces are
utilized in combination with several hours of upright posture in
``standers''. Hand in hand with loss of function is loss of
independence. The child will need help with ordinary things: associated
issues related to schooling, toileting, lifting a fork, turning in bed.
By the age of 15, the breathing apparatus of these children is severely
compromised. When laying flat in bed, these children do not have
sufficient respiratory effort to exhale, blow off CO2; hence
mechanical (noninvasive) is instituted. They sleep with a mask over the
nose and mouth (BiPap ventilation), which provides forced air into the
lungs and therefore enhances their ability to exhale. Finally, the
young man with DMD will require invasive ventilation--tracheotomy and
ventilators due to extraordinary weakness of the pulmonary apparatus.
Often we forget that muscle encompasses much more that moving bones--
the Heart is a muscle as is the Digestive tract, which is comprised of
smooth muscle. No muscle escapes degeneration in Duchenne. Children
with Duchenne have cardiomegaly (enlarged heart), decreased cardiac
output and congestive heart failure in their late teens. During the
late teens or early 20's, young men with DMD are unable to manage oral
secretions, have difficulty with digestion and require manual removal
of stool. The Diagnosis of DMD is accompanied by a lifetime of
progressive loss of function, loss of independence, dependence on
family/caregivers and extraordinary physical, mental, psychological,
spiritual and financial burden for the family and for all of us, as a
society. Finally, the loss of these boys--their absence--what we miss
as parents, siblings, relatives, communities as a society is great.
This greatest country on earth is diminished by our irreverence for the
lives of these children.
PARENT PROJECT MD
Before his death, my son Christopher asked, ``if you will not fight
for me, than who will?''. I was devastated at this question, for one
feels complete defeated when they cannot help protect their own child,
instead having to simply watch the child suffer this long, agonizing
death. Parents from around the United States, indeed the world, wanted
to advocate for their child, for this disease. In 1994, a small group
of parents founded Parent Project Muscular Dystrophy, a national
nonprofit dedicated to expediting research and cure for DMD/BMD.
Mr. Chairman, the obvious question for the Committee is, ``What can
we do?'' Parents sitting around a table in 1994 raised the following
issues, which are still valid today:
(1) How can we improve the quality of life for our children and
extend their life span?
(2) How can we initiate the development of standards of care to
provide families, physicians and care-givers access to state of the art
information and knowledge about care options to extend function and
improve the quality of life for DMD/BMD children?
(3) How can we help provide for genotyping of all DMD/BMD Children?
(4) How can specific mutations be identified and compared to
clinical progression?
(5) How can subsets of the population who have a less severe
clinical progression be identified to understand the underlying
mechanisms (compensatory) involved?
(6) Can genotypes/phenotypes be determined based on the impact of
specific regimens (steroids/nutrition/future)?
(7) Can subsets of the Duchenne population be isolated as
candidates for future clinical trial?
(8) Can the incidence/prevalence be updated? The statistic used of
1:3500 has been thrown around for years. Is it accurate? In light of
genetic counseling, are the numbers of spontaneous mutations
increasing?
(9) Is newborn screening an important goal? Would the children have
better clinical outcomes if diagnosis could be known at an earlier age?
(10) What is the role of steroids? Is there a window of opportunity
to introduce steroids? After 17 years of trials--what are next steps to
determine age of intervention/regimen--and is this outcome directly or
indirectly related to specific mutations?
(11) Can we develop strategies for identifying, supporting and
disseminating promising research and its application?
(12) What are the mechanisms required for translation of bench
research to clinical trial--FDA, Biotech, who, how? And finally,
(13) What is the Federal Investment in DMD research and advocate
for equity for children with DMD/BMD?
In 1997, Parent Project MD members initiated a legislative agenda.
Initially, we wrote letters to representatives--pleas on behalf of
their sons. In 1999, the House Labor/HHS Appropriations Subcommittee
heard our testimony. Last year, this Committee graciously included
strong DMD report language in its conference report--and we thank the
committee for this. We were further blessed to obtain a separate Title
in the Children's Health Act of 2000--the first time in history there
has been a federal mandate on DMD. This year, Valentine's Day, H.R.
717, the DMD Care Act, was introduced in the House by Representatives
Roger Wicker and Collin Peterson with 90 original co-sponsors. Parent
Project MD has established extensive collaborations with NIH and CDC,
but without adequate funding these efforts will fall by the wayside and
another generation of children will be lost to DMD.
Mr. Chairman, Congress has been very generous to NIH, and
rightfully so. But this disease--the world's number ONE lethal, genetic
disorder--gets less than 1/2000th of the resources of the NIH in
research. It is no wonder there is nothing available for these
children. Parent Project MD believes there are some structural issues
that help account for this and we would be pleased to address them.
Scientists uniformly do not believe that the peer review processes and
structure of NIH encourage muscle research. We ask that you assist us
in helping create the structural environment necessary at NIH to bring
this disease to some semblance of parity to other disease groups of
similar severity and prevalence.
Our children are not out of their warranty period before they wear
out, our children will never have the adult status to advocate on their
own behalf, our children's degeneration sends ripples of pain and
dysfunction through generations of families.
On behalf of children with DMD/BMD and their families.--We ask the
Committee to increase federal investment in DMD research and treatment.
An overall increase of $20 million per year over the course of 5 years
specifically for DMD research would change the face of this disease
forever.
Congress must do with muscle disease what it has done with many
other diseases: It must allocate this small amount of the NIH budget
specifically for research on DMD. This would jump-start an important
research field that has been chronically short on research support, and
would build the research infrastructure to an acceptable level.
TODAY, WE DO NOT SEEK EXCEPTIONAL EXPENDITURES FOR OUR CHILDREN: WE
SEEK SOME EQUITY
Respected members of the 107th Congress, today, our battle is
against Duchenne and Becker muscular dystrophy. We request EQUITY:
Equity in research opportunities, equity in set-aside funding, equity
in the review process and equity in worth, the worth of each child who
has Duchenne or Becker muscular dystrophy. We ask that you listen now
to the voices of these young men, as their voices will surely fade
before they reach adulthood. We urge you to provide the first set-aside
money for research that will investigate the territory of this
devastating disease and the weaponry needed to win this war. Without
your help, our children will continue to have the same prognosis for
another 100 years. Mr. Chairman and distinguished members of the
Committee, we are honored to appear before you today, and grateful for
this opportunity to testify.
Senator Specter. Thank you. Thank you very much, Mrs.
Furlong, for that very moving testimony. We are heartsick to
know of the death of two sons. It is a tragic loss. My wife and
I have two sons. Fortunately for us they are healthy and still
with us, but we have some understanding of your grief, and we
admire the work you are doing to try to change things for other
people's sons.
Senator Wellstone. Mr. Chairman, with your indulgence, may
I take 1 minute to just make one quick comment? I wanted Ms.
Furlong to know that really I first of all could not agree more
with what the chairman said to you, and second to know that
your work has really made a difference.
I had something to do with working on The Children's Health
Care bill, and it was because of you all that we were able to
get the language in that called for a coordinated approach on
Duchenne disease, and I think the first appropriation was just
$5 million this January, but it was a start, but before your
voices, and before the work that all of you have done, there
had not been that kind of coordination and focus, and so I just
want to make it crystal clear this is just the beginning of
this journey, but the work that you and everyone else in this
room has done has been terribly important, very, very
important. Thank you for your very strong, passionate,
wonderful voice.
Ms. Furlong. Thank you, Senator Wellstone.
Senator Specter. Thank you, Senator Wellstone.
STATEMENT OF CHRIS ROSA, Ph.D., MEMBER, MUSCULAR
DYSTROPHY ASSOCIATION BOARD OF DIRECTORS,
MEMBER, PRESIDENT'S COMMITTEE ON EMPLOYMENT
OF PEOPLE WITH DISABILITIES
Senator Specter. Our final witness on this panel is Dr.
Chris Rosa, director of the office of special services for
students with disabilities at Queens College, serves as
Muscular Dystrophy Association board of director, steering
committee of MDA national task force, earned his doctorate in
sociology from Queens College. Mr. Rosa was diagnosed with
Becker muscular dystrophy at the age of 9.
Thank you for joining us, Dr. Rosa, and we look forward to
your testimony.
Dr. Rosa. Thank you very much, Mr. Chairman. It is really
my honor to be here, along with you, Senator Craig and Senator
Wellstone. Thank you for allowing me to come before you this
morning to represent the more than 200,000 families, American
families who are affected by muscular dystrophy.
I feel that I am uniquely qualified to comment upon the
concerns of American families affected by the muscular
dystrophies, because in 1976 the lives of members of my family
were forever changed by my diagnosis of Becker's muscular
dystrophy. When my condition was first diagnosed, very little
was known about the muscular dystrophies. Doctors offered
families little hope, and prepared them for lives of diminished
opportunities, and the inevitable premature loss of loved ones.
However, over the past three decades, thanks to the work of
the Muscular Dystrophy Association, the prospects for people
with muscular dystrophy have improved dramatically. Through
MDA's national network of clinics, people with MD are receiving
the preventive health care and assistive technologies necessary
for them to live more productive lives.
Indeed, thanks to MDA, I was able to graduate from college,
to go on to graduate school, earn a doctorate in sociology,
build a rewarding career, and dream of one day starting a
family of my own. Moreover, through MDA's worldwide program of
neuromuscular disease research, we have moved to the very
threshold of treatments and cures.
While this progress is a source of tremendous hope for
families affected by muscular dystrophy, it is also a source of
great tragic irony. As those of us who have been empowered to
pursue independence by research wait desperately for effective
treatments and cures, the ravages of muscular dystrophy
continue to exact tremendous human and social costs.
Muscular dystrophy will continue to weaken vibrant,
productive people, ultimately rendering them unable to work and
forcing them to be dependent upon disability benefits. It will
continue to cut down talented, contributing members of our
society in the prime of their lives, leaving gaping holes in
the fabric of love and support that binds our families
together.
PREPARED STATEMENT
Every day, without treatments for muscular dystrophy, costs
us the very lives of dozens of bright and talented people. At
this time, we therefore propose that you respond to the urgent
need of thousands of American families by increasing NIH's
projected $19.9 million allocation annually for muscular
dystrophy research by a significant amount.
Thank you.
[The statement follows:]
Prepared Statement of Christopher Rosa
Mr. Chairman, Senator Harkin, and members of the Subcommittee, I
feel that I am uniquely qualified to comment upon the concerns of
American families affected by the muscular dystrophies because in 1976,
the lives of members of my family were forever changed by my diagnosis
of Becker MD. When my condition was diagnosed, very little was known
about the muscular dystrophies. Doctors offered families little hope
and prepared them for lives of diminished opportunities and the
inevitable premature loss of loved ones.
However, over the past three decades, thanks to the work of the
Muscular Dystrophy Association, the prospects for people with muscular
dystrophy have improved dramatically. Through MDA's national network of
clinics, people with MD are receiving the preventative health care and
assistive technologies necessary for them to live more productive
lives. Indeed, thanks to MDA, I was able to graduate from college, go
on to graduate school, earn a doctorate in sociology, build a rewarding
career, and dream of starting a family of my own. Moreover, through
MDA's worldwide program of neuromuscular disease research, we have
moved to the very threshold of treatments and cures.
While this progress is a source of tremendous hope for families
affected by muscular dystrophy, it is also a source of great tragic
irony. As those of us who have been empowered to pursue independence by
research wait desperately for effective treatments and cures, the
ravages of muscular dystrophy continue to exact tremendous human and
social costs. Muscular dystrophy will continue to weaken vibrant,
productive people, ultimately rendering them unable to work and forcing
them to be dependent upon disability benefits. It will continue to cut
down talented, contributing members of our society in the prime of
their lives, leaving gaping holes in the fabric of love and support
that binds our families together. Every day without treatments for
muscular dystrophy costs us the very lives of dozens of bright,
talented people.
We therefore propose that you respond to the urgent need of
thousands of American families by increasing NIH's projected $19.9
million annual allocation for muscular dystrophy research by an
additional $100 million.
Thank you.
Senator Specter. Thank you very much, Dr. Rosa. We hear
you, and we will take a close look at what NIH has been doing
with muscular dystrophy to see, without unduly meddling with
what the scientists are doing, if they might be of a mind to
have some reallocation.
Mr. Decker, I noted early on your comment about, or in your
bio, you participated in gene therapy, first patient to undergo
gene therapy. What was that like, and what were the results?
Mr. Decker. Like I stated in my testimony, the results are
not known yet. I did speak to Dr. Mandel last week because I
thought it would be nice to have the test results for this
hearing, but he advised me that in about a month or so the test
results should be out.
As far as what it was like, it was a dream come true,
because we went from 20 years ago, never knowing if there would
be a cure, to where I am very optimistic on how things are
going to go. Dr. Hansel Stedmans, who is in the audience today,
was one of the researchers there, along with Dr. Jerry Mandel.
You could not ask for any better doctors to be involved with.
The Ohio State University was extremely--I cannot say enough
about everybody there.
Being selected, because of the right genetic disorder was--
it is very humbling. As far as which foot do I think the new
gene was in, I do have my opinions, but the doctors tell me
that the dosage was so low, set by the FDA, that they did not
figure I could realize which foot it was in, but I do think I
know which foot the new gene was in, and the muscle biopsies
were taken 6 weeks after the injections, just like everything
went, but I must stress the goal of the first phase is safety
only.
They have done one patient other than myself. Neither one
of us had ever had any soreness of the feet, and I have
remained in contact with the other person, and they do feel
that they know which foot the new gene was in, too.
Senator Specter. Thank you very much, Mr. Decker.
Senator Craig.
Senator Craig. Well, thank all of you for being here today
and your testimony and your willingness to come forward and get
involved. I think, Dr. Rosa, your statement about tragic
ironies speaks well for all of you.
Ms. Furlong, H.R. 717, if it were to become law, would
authorize three centers of excellence for DMD research at the
NIH, and it authorizes three centers of excellence for DMD,
data collection surveillance, epidemiology--would you give us a
little of the background of your involvement of why the
legislation was structured as it was, and do you believe it
fills the needs that we currently understand, or you currently
understand are there?
Ms. Furlong. Yes, I would love to address those issues. The
term, 1 in 3,500 male children worldwide, has been used for a
very long time. The Parent Project Muscular Dystrophy Project
has had questions about that.
If, for instance, two-thirds of that disorder is by
familials, from families, and one-third is spontaneous
mutation, one would assume that with genetic counseling, you
could tip the scales so that the incidence would be less. It
does not occur to us that the incidence is less, so one of the
questions that we would like the Center for Disease Control to
approach, or to ask, is, is the incidence of 1 in 3,500
accurate? Has it changed?
There has been a German study in 1997, and from the numbers
of the German study, if you do the math, you could get the
number 1 in 2,500, which certainly changes the incidence, and
prevalence of the disorder, and certainly the need for
research, so these are the questions, to start at the beginning
and look at what incidence and prevalence, and finally--not
finally, but in the process to look at the standards of care
for these children, and make them consistent across the board.
When my sons were diagnosed, we visited five doctors in the
course of the next 30 days. I must tell you that that is such a
devastating blow that you are willing to try anything, go
anywhere, and in those physicians we visited, and the same is
true today, there was a wide degree of what might be
appropriate in terms of these children, and perhaps it is
related to the age of diagnosis, and, further, the mutation,
the specific mutation of the child, so we need to know those
things, what is the standard of care, will it vary for a child
with a different mutation, and if there is a child or a young
man with a different mutation that is doing very well, could we
apply that compensatory mechanism, for instance, to the
children who are not doing so well, to make them improve in
their outcomes, so there are a certain number of questions that
we think the bill addresses.
We also think that in your home State, Senator Specter, you
have some very fine institutions, the University of
Pennsylvania, University of Pittsburgh, with some very fine
research. There are amazing scientists. The Muscular Dystrophy
Association has developed a remarkable basis of information,
and many of these people are collaborative, at the same
institution.
Centers of Excellence create a critical mass. There is
Washington, D.C., with Dr. Eric Hoffman, who is here. There are
such critical masses that you could really isolate some sets of
collaborators to do specific jobs to approach this
systematically to improve the prognosis and life span of these
young men, hence the bill.
Senator Craig. Thank you. Thank all of you very much.
Senator Specter. Thank you, Senator Craig. Thank you very
much, Ms. Furlong, Dr. Rosa, Mr. Decker. We hear you, and we
will try to help even more.
STATEMENT OF JERRY LEWIS, INTERNATIONAL ENTERTAINER AND
NATIONAL CHAIRMAN, MUSCULAR DYSTROPHY
ASSOCIATION
ACCOMPANIED BY BENJAMIN CUMBO, MUSCULAR DYSTROPHY ASSOCIATION'S
NATIONAL GOODWILL AMBASSADOR
Senator Specter. I would like now to call Mr. Jerry Lewis,
at the center of the American stage for more than 50 years, a
great humanitarian, striving to provide his kids with a better
future. He has led the worldwide fight against neuromuscular
disease as national chairman of the Muscular Dystrophy
Association. He battles on behalf of more than 1 million
Americans affected with these diseases.
Since 1966, his Labor Day Telethon has raised over $1
billion for muscular dystrophy. His honors are legendary, and
include being nominated for the Nobel Peace Prize, the only
entertainer ever nominated for this honor, and received a
Lifetime Achievement Award from the American Medical
Association, the U.S. Defense Department's highest civilian
award, the Medal for Distinguished Public Service, and
accompanying Mr. Lewis is Mr. Benjamin Cumbo.
Mr. Lewis, Jerry Lewis, thank you for all you have done.
Thank you for coming here today.
Mr. Lewis. My pleasure. Thank you.
I have to tell you that I got in the elevator to come here,
and this cute lady that works in the Senate was in the elevator
when I got on and she said, you're Jerry Lewis. I said, no, I'm
not. She said, yes, you are. I said, no, I'm not. She said, you
are. I said, okay, I am. She said, no you're not.
I thank you, Senator Specter and Senator Craig, for this
opportunity. I think that I have to mention the fact that most
everything I have done in the 50 years working with MDA and
working for my kids, I have never in 50 telethons ever read
anything, other than possibly a scientific piece of data, but
for the most part everything has come from my heart, and I
think that is why the American people have been so responsive.
But because this is so vital today, I am going to do
something I have never done before. In truth, it is the first
time. I am going to read the text exactly as we put it
together, because it is all too important, so if I am looking
down a couple of times, I am not ignoring you, Senator. It is
just that I am reading, which I learned to do many years ago.
I am grateful for this opportunity to speak on behalf of
the quarter million Americans affected by muscular dystrophy. A
quarter million. That is a big number. So you can put a face on
this problem and understand in human terms why we are all here,
I brought a short video for you to watch. Please, if you will.
Ben is now 13. He was MDA's National Goodwill Ambassador in
1996. He is what this is all about, and our presence here
today.
For 50 years, I have been fighting an evil, insidious force
that preys on people like my pal Ben. I vowed all those years
ago that I would beat muscular dystrophy in my lifetime. I will
be 75 in 3 weeks, and I am a tough bird, but don't you think
that at this point I cold use a little help?
Since 1950, the Muscular Dystrophy Association has been out
there leading the charge against all nine forms of muscular
dystrophy, not just Duchenne muscular dystrophy, about which
you have heard a great deal today. Virtually every major
discovery in these diseases was funded by MDA.
We have located the genetic defects for almost every form.
We have tested countless drugs and compounds looking for the
answers. We have developed techniques that are being used in
the battles against scores of other diseases. We did not ask
the Government for help, because we could do it alone. We did
not need help.
My message to you today is this: Things change. Today, we
need the help. MDA has laid all the groundwork. Now it is time
to take what we have learned, this vast well of knowledge, and
turn it into treatments and cures. We have worked so hard,
received so much support from the American people it is
incredible. It would be a tragedy and a sin for our march
toward victory to be stalled now.
We are actually the victims of our own success. MDA has
done such an outstanding job of providing vital services and
directing revolutionary scientific research that everyone,
including the Government, thinks we can do it all. Well, I am
here to tell you we cannot, not any more. The clinical trials
that we must conduct to test the things that we think could
stop muscular dystrophy are expensive, unbelievably expensive.
Without Government support, many trials will never happen, and
those that do will take much longer.
This is unacceptable. I cannot tell a quarter million
Americans that they are not a national priority. For years,
Government research on muscular dystrophy was underfunded
because everyone counted on MDA to carry the load. This has
allowed a lot of money to go to research in other diseases.
You have heard testimony about how diseases affecting far
fewer people get much greater funding through the National
Institutes of Health. It is time for the quarter million
Americans that I have the honor to represent to get their fair
share. They waited long enough, and they deserve it. That is
why I am asking for $100 million annual increase in NIH funding
for muscular dystrophy research.
Now, I know what you are thinking. This crazy comedian is
asking for the world. No, I am not, not really. I am only
asking for the weapon that we need to win the war against
muscular dystrophy. I do not believe anyone would think a
quarter million Americans represent acceptable casualties. I do
not think the loss of even one is acceptable.
Other witnesses here today have given you all the facts and
figures you need to justify another $100 million for muscular
dystrophy research. When it comes to those I fight for, I do
not think in terms of facts or numbers. I think in terms of
children, of mothers, fathers, or brothers and sisters. That is
what this is all about, and has been for 50 hard years.
PREPARED STATEMENT
I carry in my heart the memory of every person with
muscular dystrophy I have ever met. I hope you will carry the
image of Ben, both the little boy and the young man, in your
hearts when you consider this request. If you do that, I know
you will do right by Benjamin and all the kids.
Thank you for your time.
[The statement follows:]
Prepared Statement of Jerry Lewis
Mr. Chairman, Senator Harkin and members of the subcommittee, I'm
grateful for this opportunity to speak on behalf of the quarter million
Americans affected by muscular dystrophy. A quarter million--that's a
big number. So you can put a face on this problem and understand in
human terms why we're all here, I've brought a short video for you to
watch.
That cute little boy in the video is now the handsome young man
sitting to my (right/left). Benjamin Cumbo, now 13, was MDA's National
Goodwill Ambassador in 1996. He's what this is all about.
For 50 years, I've been fighting an evil, insidious force that
preys on people like my buddy Benjamin. I vowed all those years ago
that I'd beat muscular dystrophy in my lifetime. I'll be 75 next month.
Now, I'm a tough old bird, but don't you think that at this point I
could use a little help?
Since 1950, the Muscular Dystrophy Association has been out there
leading the charge against all nine forms of muscular dystrophy, not
just Duchenne muscular dystrophy about which you've heard a great deal
today. Virtually every major discovery in these diseases was funded by
MDA. We've located the genetic defects for almost every form, we've
tested countless drugs and compounds looking for the answers, we've
developed techniques that are being used in the battles against scores
of other diseases. We didn't ask the government for help because we
could do it alone. We didn't need help.
My message to you today is this: Things change. Today, we need the
help. MDA has laid all the groundwork. Now it's time to take what we've
learned--this vast well of knowledge--and turn it into treatments and
cures. We've worked so hard, received so much support from the American
people, it would be a tragedy, a sin, for our march toward victory to
be stalled now.
We're actually the victims of our own success. MDA has done such an
outstanding job of providing vital services and directing revolutionary
scientific research that everyone, including the government, thinks we
can do it all. Well, I'm here to tell you, we can't. Not anymore. The
clinical trials that we must conduct to test the things that we think
could stop muscular dystrophy are incredibly expensive. Without
government support, many trials will never happen and those that do
will take much longer. This is unacceptable. I can't tell a quarter
million Americans that they aren't a national priority. For years,
government research in muscular dystrophy has been underfunded because
everyone counted on MDA to carry the load. This has allowed a lot of
money to go for research in other diseases. You've heard testimony
about how diseases affecting far fewer people get much greater funding
through the National Institutes of Health. It's time for the quarter
million Americans that I have the honor to represent to get their fair
share. They've waited long enough and they deserve it. That's why I'm
asking for a $100 million annual increase in NIH funding for muscular
dystrophy research.
Now, I know what you're thinking. This crazy comedian is asking for
the world. No, I'm not. I'm only asking for the weapon that we need to
win the war against muscular dystrophy. I don't believe anyone would
think a quarter million Americans represent acceptable casualties. I
don't think the loss of even one of ``my kids'' is acceptable.
Other witnesses here today have given you all the facts and figures
you need to justify another $100 million for muscular dystrophy
research. When it comes to ``my kids,'' I don't think in terms of facts
or numbers, I think in terms of children, of mothers, of fathers, of
brothers, of sisters. That's what this is all about and has been for 50
years. I carry in my heart the memory of every person with muscular
dystrophy I've ever met. I hope you'll carry the image of Benjamin,
both the little boy and the young man, in your hearts when you consider
this request. If you do that, I know you'll do right by Benjamin and
all ``my kids.''
Thank you and God bless you all.
Senator Specter. Thank you very much for that very poignant
and moving testimony, Mr. Lewis. We thank the Cumbos for being
with us today, and for bringing Benjamin along.
Ben, you are not scheduled to have a speaking part, but let
me ask you how you are.
Mr. Cumbo. I am doing all right. I am just a regular 13-
year-old boy just trying to do everything I can, just trying to
get a girlfriend, too.
Listening to hip-hop, and everything a regular teen boy
will regularly do, but me, I just realize that I am extremely
lucky, and God has blessed me because I mean, there are people
that are a heck of a lot worse than I am, and I mean, don't
just do this for me, though. I mean, there are other people in
worse condition than I am, and if they can get funding, too,
from NIH, this will be great right here, because if the
Government can spend, like $2 billion on one plane, and stuff
like that, $100 million will not hurt for 5 years.
Mr. Lewis. Good boy, Ben.
Senator Specter. Ben, have you considered being a Senator?
Mr. Cumbo. I don't know. I just--I mean, with your help I
hope I can pursue a career in the military as pilot, I guess,
hopefully.
Senator Specter. Well, we may have to reserve one of those
$2 billion planes for you.
Ben, how are you feeling? Are you feeling okay?
Mr. Cumbo. Oh, yes, I am feeling very fine.
Senator Specter. Are you able to participate in sports?
Mr. Cumbo. Unfortunately, no. I mean, I used to, as you can
see in the video that they just displayed earlier, but I mean,
now I am getting a little weaker though, and I am not really
able to do that, but one thing I can concentrate on is just
being a good student and just trying to do the best thing I can
with everything I can.
Senator Specter. But you are doing okay with the girls?
Mr. Cumbo. I don't know yet. I mean, I might have to wait,
like, 3 more years. I don't know.
Senator Specter. Well, Ben, we thank you for coming here,
and we thank your parents for making the video, because you
bring to life the exact nature of the problem, and we hear you.
Jerry Lewis, we have watched you for years and years and
years and years, and we have all seen your telethons, and we
marvel at how you do them. How long do they last, more than 24
hours?
Mr. Lewis. Well, including prep time they run about 38
hours.
Senator Specter. 38 hours?
Mr. Lewis. Yep.
Senator Specter. Well, that is a phenomenal physical
exercise.
Mr. Lewis. There is no ham in my family. I got it all.
Senator Specter. We are going to take a look at the NIH
budget on muscular dystrophy. The National Institute for
Neurological Disorders gets slightly under $1.2 billion, and
muscular dystrophy is slightly under $20 million, and there was
an increase last year of almost $147 million for the
neurological institute. The NIH has been very, very expansively
and expensively funded, and as you might suspect, the Congress
does not make the allocations, but I think that NIH will hear
what you said today. Dr. Penn will hear what you said today--
she is nodding in the affirmative--and we have a couple of
other experts. A little oversight by the scientists of the
scientists is always a very healthy thing.
Mr. Lewis. Senator Specter, may I make a point----
Senator Specter. Sure.
Mr. Lewis [continuing]. About the fact that NIH had a
budget of $19.9 billion, came to that particular figure
relative to muscular dystrophy research over a period of years,
over the period of years of survey, examination, plotting, and
planning, that figure came into play.
Since that time, we now are into genetic engineering. We
are into DNA. We are into trials where we know the answer will
come from. We are talking about $5 million a trial. We will use
20 trials in the first year after you give us the $100 million,
and then we are going to have to look forward to the following
year, when you do it again.
But we could ostensibly get the answer in the first series
of trials, so what I am saying is, the Government of this
country can put the cherry on the cake of the 50 years that I
have put in. Please think about that cherry.
Senator Specter. Well, it is a very important matter. There
is no doubt that you are representing, Ben is representing a
lot of youngsters stricken with muscular dystrophy, and we do
hear in this committee hearing room situations involving many,
many tragedies, but none more important than muscular
dystrophy.
Mr. Lewis. And your two sons, Senator, that you alluded to
earlier, are healthy, thank God, because of the work we do and
have done in the 50 years. We have not the faintest idea how
many innocent human beings have been saved by the work we have
done, and that is a very, very strong comment, along with what
we are talking about today.
Your sons are healthy, thank God, and what we do is to keep
them from ever becoming my kids, so if the good Senate will
look at this carefully--and I mean expeditiously, simply
because we are dealing in life and death, and the answers, the
sooner they come, we will get to the victory dinner quicker.
Senator Specter. Well, having identified the gene in 1987,
I would like to have some answers as to what has been done in
the intervening 14 years. That is a long time.
And we have to mount a very intensive campaign on stem cell
research, which may hold the key----
Mr. Lewis. Right.
Senator Specter [continuing]. For muscular dystrophy, as it
appears to hold the key for many, many other ailments.
But this turn-out today has been a very impressive one. We
thank all of you for coming. We feel the emotion and the
electricity in the room, there is no doubt about it, and
Senator Craig, you can have the last word.
Senator Craig. Well, thank you, Mr. Chairman. No, I am
going to give Jerry Lewis the last word. He deserves it for the
commitment and dedication you have had, but you know, Mr.
Lewis, I think Benjamin upstaged you today----
Mr. Lewis. Absolutely.
Senator Craig [continuing]. In a way that I know you will
accept.
Mr. Lewis. Yes, absolutely.
Senator Craig. The young man sitting beside me here from
Lafayette, California, he tells me it is north of San
Francisco. He just slid me a note a few moments ago and said,
you have got a very interesting and hard job.
His name is Scott, and Scott is right, we have a
fascinating job, but it is a tough one. I am extremely pleased
that Congress has committed itself to rapid increases in money
that has gone to NIH in the area of health and medical
research, and we will try to continue to do that. We are
beginning to recognize the benefits, and humanity is beginning
to feel them. We would like to see results.
Mr. Lewis. You will all be blessed, Senator Craig.
Senator Craig. Well, what you have done and what all of
these parents and this organizational work has done over the
years--and you have said it well: It has set us up in a
positive way. I will certainly work with Chairman Specter to
see where we can get, both in money and in the structure
necessary--the legal structure necessary to see if we cannot
accomplish some of these things.
We as a country are blessed right now, in the sense that we
have some resources. It is a matter of prioritizing. There are
a lot of diseases out there, and all of them bring to us tough
choices. Our resources are substantial, but they are limited.
We will sort them out. Your presence here today, and the
presence of all of you and these marvelous parents and young
people send a very loud message. Thank you.
Senator Specter. Thank you, Senator Craig. Thank you, Ben,
thank you, Jerry, and thank you all.
Mr. Lewis. Thank you, Senator.
Additional Prepared Statement
Senator Specter. The subcommittee has received the prepared
statement of Jeff Baxter on behalf of the Parent Project MD.
The statement will be placed in the record.
[The statement follows:]
Prepared Statement of Jeff Baxter
Mr. Chairman, I would like to begin by thanking the Committee for
hosting today's hearing on this important children's health issue--and
for inviting me to speak on behalf of the Parent Project MD, and more
importantly for allowing me to speak for those who don't always have a
voice in the political process--little boys with Duchenne Muscular
Dystrophy.
Mr. Chairman, as a professional musician and guitar player, I have
made a life's work of playing the guitar and making music. My
profession requires me to use all my muscles on a daily basis--to play
the guitar, to sing songs, to dance, to perform. I am ashamed to admit
that I take my capabilities for completing these daily activities for
granted. I can't imagine what it would be like to not be able to play,
to sing, to dance, or to perform.
Unfortunately, children with Duchenne are so physically limited,
that they will never have the opportunities I've had. We have
distinguished medical professionals here today who can tell you all of
the scientific and technical reasons why this is the case. But, I'm
here to be the voice, the hands, and the legs for those boys who have
no voice, no strength in their hands, no power in their legs. Children
who have such difficulty raising their arms to feed themselves and
lifting their legs to walk, that they can't even think about playing an
instrument, dancing on stage, or performing for a crowd. Children who
by the age of 14 need major surgery to stabilize their spine and a
ventilator to breathe. Mr. Chairman, when these kids are at the age
when they should be worrying about college, listening to the music,
hanging out with their friends and enjoying and all the passions of
youth--these boys are already gone.
Mr. Chairman, you may wonder why I'm here today? Well, I'm here for
my friend's son Bill, an 11-year old with Duchenne, and all the boys
suffering with this deadly disease. For now, Bill is doing as best as
one can expect given his predicament--he can still walk, although even
the smallest stair is a struggle. And he is the exception, because the
majority of DMD cases are in a motorized wheel chair by the time they
are Bill's age.
Bill is a bright little boy whose future is already mapped out in a
defective gene--he won't play the guitar, he won't ever perform on
stage, he will never be able to have children of his own . . . he and
the other boys will never know their full potential because this
disease is killing them.
Mr. Chairman, I'm here today to make a statement and plead a cause.
Help Bill and the thousands of other children with Duchenne muscular
dystrophy. Help these boys live. We have got to get serious about
research, and it requires a commitment from the private sector, from
people like myself, and from the federal government. I've helped the
Parent Project Muscular Dystrophy raise some funds, but this is just a
drop in the bucket for what is required for true progress. We need your
help and the help of the NIH and CDC to get organized to fight this
disease. Mr. Chairman, help me help the boys with Duchenne.
Let me end by reiterating how honored and grateful I am to be here
today, and I applaud the Committee for holding this important hearing
and giving me the opportunity to speak for the Duchenne boys.
CONCLUSION OF HEARING
Senator Specter. Thank you all very much for being here,
that concludes our hearing.
[Whereupon, at 11:55 a.m., Tuesday, February 27, the
hearing was concluded and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]