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the elderly. As you know, our investigators discovered a faulty gene in a particular familial form of osteoarthritis. This arthritis occurred in youngsters. The scientists were able to identify, in a family of three generations in which nine of the members developed severe osteoarthritis in their twenties, this specific fault in the gene for collagen II. Collagen II is a molecule of 1,000 amino acids. They found the fault in a substitution of only one of these amino acids for another. This provides a new direction for research on osteoarthritis generally, and this work is now beginning.
The second spectacular discovery is that of research in using transgenic animals to study the spondyloarthropathies. This is a group of diseases associated with arthritis of the spine and other joints and other manifestations. This is a common disease of young men, perhaps the most common form of arthritis in young men. It had been found that there is a tissue type, HLA-B-27, that was associated with these diseases. It had been suspected that certain infections actually initiate these diseases. There had been some question about the importance of genetics. With this transgenic mechanism, they have been able to take the human B-27 gene, inject it into the fertilized egg of in-bred rats, and then reproduce the whole human disease. This establishes a clear role for genetics in these forms of arthritis. Spectacular.
We also have interesting work going on in lupus. Lupus, as you know, is nine times more common in women, three times more common in black women than white women. We have a whole task force to look into why this is so and what we could do in educating those at special risk.
Finally, we have made giant steps in developing our national research plan. I believe we advised you last year that it was going to take us about 2 years to develop that plan. We are clearly ahead of that schedule. We had a national task force meet in February, north of Baltimore, with 140 of the leading scientists in the Nation, in five different disease areas, Senator Harkin. We had five science panels with anywhere between 22 and 35 leaders each in arthritis, muscle biology, bone biology and bone diseases, musculoskeletal, orthopedic disease, and dermatology; and nine crosscutting issues panels. They have come up with a research plan in draft of about 1,000 pages, with very exciting recommendations for the future. It will take us a few months to complete the final report of the national plan, and we will be glad to submit it to you then.
That is our report, sir.
STATEMENT OF DR. LAWRENCE D. SHULMAN
The National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) supports a broad range of basic and clinical research on many of the
most debilitating diseases affecting the health of the Nation.
I am privileged
to discuss with you some of the scientific advances that have been made this
past year in the disease areas under the mandate of the Institute, and to share
with you some of our future plans,
Osteoporosis, the leading cause of bone fractures both in postmenopausal
women and in the elderly, affects approximately twenty-four million Americans.
The NIAMS leads the federal research effort to conduct and support basic,
bisphosphonates--was shown to be very effective in combatting the bone loss of
The Institute continues to expand its research efforts in osteoporosis.
Two requests for applications (RFAs) for research on osteoporosis are being
One invites additional basic research on fundamental causes.
second invites more grant applications on clinical and epidemiological research
The Institute is also stepping up its disease prevention and
health promotion efforts with regard to osteoporosis.
The NIAMS Information
Clearinghouse will expand its educational activities both for the public and
for health professionals.
Projects to inform consumers about risk factors,
preventive measures, and research results are being planned.
There are more than 100 kinds of arthritis, affecting not only the joints
but other connective tissues of the body including important supporting
structures such as muscles, tendons, and ligaments.
One of the most common is
rheumatoid arthritis, a chronic inflammatory disease afflicting more than 2
million adults in the United States.
In recent experiments with rats,
scientists have developed a T-cell vaccine that could ultimately lead to T-cell
therapy and vaccination in humans.
The Institute has also begun a clinical
trial in which an antibiotic is being tested as a treatment for rheumatoid
In other recent research, a dissimilarity in tissue type between
mother and fetus has been found in many women with rheumatoid arthritis who
improve during pregnancy.
This finding suggests that the mismatch induces an
immunologic reaction that suppresses the arthritis.
Lyme disease, which has both arthritis and skin disease among its major
manifestations, has become a national problem.
It is now the most common
insect-borne disease in the Nation, and its distribution is worldwide.
is giving high priority to both research and outreach programs for Lyme
The Institute has recently funded several new basic research grants
to increase understanding of how the infectious agent causes the disease,
the hopes of improving diagnosis and treatment, and providing the foundation
for development of an effective vaccine.
NIAMS is also supporting a clinical
trial to determine if antibiotics can prevent Lyme disease from emerging in
people who have been bitten by the deer tick.
Programs to better inform both
the public and health professionals about the dangers and prevention of Lyme
disease are under way.
A data base on educational materials was recently
completed; and in early March 1991, a workshop on Lyme disease will be held
with panels of experts to develop up-to-date vital information for physicians
on both the diagnosis and treatment of Lyme disease.
One of the most exciting breakthroughs this year was the identification of
a gene that causes a form of osteoarthritis, the most common form of arthritis,
a disease in which the cartilage that covers and cushions the joints breaks
NIAMS-supported investigators at two different grantee institutions,
working together, isolated and characterized a faulty gene for collagen II, the
main structural protein that strengthens cartilage.
Another exciting breakthrough in arthritis this year was the successful induction, by transgenic transfer, into inbred rats of both the human gene
(HLA-B27) for spinal arthritis and the entire clinical spectrum of the group of
diseases (spondyloarthropathies) associated with spinal arthritis.
found in over 90 percent of patients with spinal arthritis, and in only 8
percent of the general population.
These diseases associated with spinal
arthritis comprise the most common forms of arthritis in young men.
striking mimicry between the disease manifestations found in this animal model
and those found in humans opens avenues for research, including the testing of
innovative therapies, that were unimaginable just a few years ago.
NIAMS epidemiological investigation of Native Americans in Alaska and Siberian
Eskimos--populations that have a high prevalence of spondylitis .promises to
shed light on the roles of genetic factors and environmental triggers, such as
Systemic lupus erythematosus (lupus) is an immune-mediated inflammatory
disease that afflicts numerous Americans, largely young women, especially black
women of child bearing age.
The disease affects the skin, joints, kidneys,
brain, and other organs.
Recently, a new antibody was identified that is
clearly associated with psychiatric disorders due to lupus; this antibody will
make better diagnosis possible.
The Institute has set up a task force to study lupus in high-risk
with advice from the task force, NIAMS is developing instructive
kits that will help health care providers and community organizations conduct
health promotion programs targeted to young black women.
The Institute also
plans to sponsor an international workshop on systemic lupus erythematosus to
assess current knowledge and develop directions for future research.
Scleroderma is a serious disorder of connective tissue and the fine blood
Besides damaging the skin, muscles, and joints, the disease may also
affect internal organs, such as the kidneys, heart, and lungs, making it life.
threatening in some people.
Women are affected three times more often than
The first symptom of scleroderma is usually Raynaud's phenomenon, wherein
blood vessels in the fingers narrow as the result of vasospasm, causing the
hands to become pale and cold.
There is also pathologic evidence of vascular
disease seen under the microscope.
Accordingly, there is keen interest in
exploring vascular abnormalities that may contribute to the etiology of the
NIAMS will issue a program announcement to stimulate more research on
causal mechanisms in scleroderma.
Over 100 different conditions are included among the heritable connective
tissue disorders, all of which stem from abnormalities of connective tissue,
the scaffolding that girds bone, skin, blood vessels, and the protective
coverings of internal organs.
Although the disorders are uncommon, they are
In April 1990, NIAMS cosponsored a multidisciplinary
scientific workshop on heritable connective tissue disorders.
participants made it clear that sophisticated research methods are enabling
scientists to unravel the complex biology of connective tissue and to uncover
the several defects that cause the disorders.
The Institute is encouraging
additional research in this area,
and is exploring the possibility of a patient
registry to facilitate progress against these diseases.
Reducing the risk of sports injury is important to millions of Americans
who participate in exercise programs and athletics.
The Institute's mission
includes responsibility for research on exercise physiology and sports
Basic facts about how muscles function at the molecular level
now being discovered.
Recent research has revealed a mechanism by which a
serious knee injury can destroy a joint.
In April 1991, the Institute, in
concert with the National Advisory Board, will hold a workshop on scholastic
sports injuries to monitor the causes of athletic injuries and identify ways to
We are continuing to make progress in research on the numerous skin
diseases that affect so many Americans.
In epidermolysis bullosa, a
devastating inherited blistering disease that affects the skin and mucous
membranes, researchers have found that the anchoring fibrils-- which link the
outer layer of the skin to the inner layer--are conspicuously absent or
Recent investigations have also shown that type VII collagen, the
major structural protein of anchoring fibrils, can be broken down by both
collagenase and gelatinase.
Other research, utilizing patients assembled by
the National Epidermolysis Bullosa Registry, suggests that abnormal synthesis
of type VII collagen be responsible for the reduced number of anchoring
Alopecia areata is a disease of the hair follicle that results in patchy
or total loss of hair.
The psychological impact of the disease can be
debilitating, especially in young people.
In October 1990, NIAMS and the
National Alopecia Areata Foundation sponsored a 2-day research workshop on the
Experts in a wide variety of areas were convened for an open exchange
of information on clinical and histopathologic features of alopecia areata,