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physicians of existing knowledge of medication effects in older persons would help reduce this problem.

However, more information on geriatric pharmacology is also critically needed. For fiscal year 1991, NIA issued a Request for Applications on geriatric pharmacology, aimed at better medication use for older persons. NIA received 114 applications and was able to fund 12 of these projects, including two clinical trials of techniques to improve drug prescribing, and several studies aimed at improving current drug therapy and identifying adverse effects.

Though these projects are a significant beginning, the current extent of research only addresses a small fraction of undiscovered drug effects and interactions in older persons. We also need research-based guidelines for the withdrawal of medications from older persons, so that only those medications required are continued. Since multiple medication use is so common among older persons, expanded efforts in these areas are needed.

Perhaps even more fundamentally, we need better medicines which will not have the adverse effects of many drugs currently used for health problems of older persons. Treatments which could correct underlying age-related debilitating conditions rather than merely their symptoms could increase benefit and lessen risk.

A particularly promising prospect is the use of trophic factors such as growth hormone. Trophic factors are hormones and other factors in the body which promote growth or maintenance of tissues. Interest is rapidly increasing in their potential to arrest or reverse degenerative changes in bone, muscle, nerves, and cartilage which lead to frailty and dependence. A recent short-term study in Chicago and Milwaukee, showing that growth hormone reverses such changes in certain older subjects who have low levels in their blood, raised the issue of a "fountain of youth" in the more sensational press. While growth hormone is clearly no such panacea, and much more testing is needed to determine its clinical value and safety, the excitement over this study captures trophic factors' great potential for fundamental progress against degenerative conditions long considered inevitable with advancing age. Possibilities for additional research are rapidly expanding and need to be pursued, particularly because clinical tests as well as laboratory studies are now feasible.




Senator HARKIN. The subcommittee will resume its sitting.

Dr. Shulman, welcome back. It is always a pleasure to see you and have an opportunity to learn more about the Institute and its research programs. I understand that April 16 is the fifth anniversary of the founding of the National Institute on Arthritis, Musculoskeletal, and Skin Diseases. I must congratulate you on the tremendous contribution the Institute has made these past 5 years, both to the scientific research community and to those who suffer from these chronic diseases. Although much has been accomplished during this time, I know that you feel there is still much to be done.

I see that the Institute's 1992 budget request is $204.8 million, an increase of 6 percent over last year's appropriation.

Could you please briefly summarize the Institute's five science programs and highlight your plans for fiscal year 1992 in these areas, Dr. Shulman?

Dr. SHULMAN. Thank you so much, Mr. Chairman. Mr. Chairman, our Institute is having a very good year this year. We are supporting some exceptional research with some key discoveries. We have had excellent workshops, new developments in our intramural program, and we are developing new initiatives, as you and we have identified them this past year.

Prevention is the key. We agree with you on that point.

We work on diseases that concern women's health, minorities, and rare diseases as well. We have many of the diseases in that rare disease category that we are interested in.

OSTEOPOROSIS However, let's start off with osteoporosis, for which, as you know, we are the lead Institute. We have had much progress this year in osteoporosis, but we have a great deal more to do. We prepared a major report for the Department to submit to you on osteoporosis. I demonstrate it here. It is a very fine report, and we are pleased to have had the privilege of doing it. Many suggestions for the future research are in that report.

In response to your request for special emphasis in this area in the amount of $6 million during the current year, we have issued two requests for applications, one for basic research on causal mechanisms on osteoporosis, and the second on clinical and epidemiological research. We have also joined with the Aging Institute in another request for applications in interventions in the elderly who have osteoporosis.

In the meantime, we have had some research advances in osteoporosis. A key one, as you know, are the bisphosphonates which are used to retard bone loss in post-menopausal women. It provides an alternative to estrogen replacement therapy, which has been confirmed once again as being valuable. We need to find the best type of hormone combinations for that effort.

Calcium is important at all ages. Let me indicate that we have had a very interesting study this year in young twins, children. Some twins have been taking the ordinary amount of calcium that children are supposed to take; their twin pairs have taken a supplement of twice that much. Those who have taken the supplement have built up more dense bones than the others who have taken the ordinary amount.

We have had a study report in the New England Journal of Medicine of women who are not producing the normal amount of hormones during their twenties, thirties, and forties; they have lower bone mass than other women who menstruate normally.

We have also had studies showing that running in the elderly may actually be helpful.

The right amount of exercise is a problem not only for all of us, but especially for our astronauts. Senator HARKIN. Excuse me. Did you say running?

Dr. SHULMAN. Older people running. It is good for them, good for their bones.

Senator HARKIN. Thank you. Now, I have it clear in my head. It is good for older people to run. All right. (Laughter.]

Ďr. SHULMAN. It's good for their bones. This is a problem for our astronauts. If we are going to go to Mars, either with or without the Soviets, we have to be sure that the astronauts don't lose much of their bone mass. So, we are working with NASA on this.

LYME DISEASE Another area of importance that has interested both you and us is Lyme disease. We appreciate that this disease is still spreading. Last year, as you know, we issued a request for applications on causal mechanisms. With your special emphasis this year, we have responded with another request for applications, this time for research on the diagnosis and treatment of Lyme disease, both of which are still problems. We have keen problems in the diagnosis of Lyme disease. There is difficulty in defining it with great accuracy, and we do not have fully reliable laboratory tests. Various tests do not agree with one another, according to a study done by the CDC and as reported at a conference last fall.

There seems to be both underdiagnosis and overdiagnosis in endemic areas. So, this is another type of problem. And certain outdoor workers, such as forestry workers, are actually at special risk, and we need to have preventive modes for them.

OSTEOARTHRITIS We have had exceptional discoveries in two areas. The first is osteoarthritis, the most common form of arthritis usually occurring in 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.
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