[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

                               __________

         Printed for the use of the Committee on Appropriations


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

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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

                              ----------                              
                                                                   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

                              ----------                              


                       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.]

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