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FY 2005 Statement to the House and Senate Appropriations Subcommittees
April 1, 2004 (historical)
Stephen I. Katz, M.D., Ph.D., Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
William Beldon, Acting Deputy Assistant Secretary, Budget
Mr. Chairman and Members of the Committee:
I am pleased to present the President's budget request for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The fiscal year (FY) 2005 budget includes $515.378 million, an increase of $14.470 million over the comparable FY 2004 appropriation.
This has been a very productive year for research in our mission areas, and I want to now share with you highlights of some of the advances and initiatives that researchers supported by the NIAMS have accomplished this year.
While we have known for many years the value of translating findings from the laboratory setting to benefit public health, the explosion of knowledge and availability of remarkably sophisticated tools over the last several years make the translation of research even more important in the many and diverse diseases that affect bones, muscles, joints, and skin. It is noteworthy that this increase in knowledge and tools was created in large part as a result of the significant budget increases that the NIH received from the Congress for this vital work. The importance of translational research is best illustrated by an actual example of a recent scientific advance in our knowledge about the immune system. A decade ago, scientists working in the Intramural Research Program of our Institute discovered a particular protein, an enzyme that they called JAK3, and they determined that it was found only in immune system cells. They would never have suspected at that time of discovery that this finding would hold great promise for people undergoing organ transplantation, as well as the millions of people affected by the vast array of autoimmune diseases. Because JAK3 is essential for immune cell function, and because its expression is limited to blood cells, researchers predicted that the inhibition of JAK3 could provide a new avenue of drug development for immune system suppression. Immune system suppression is important in treating autoimmune diseases, and it is also highly desirable in people who have received organ transplants - so that the body will not reject the new organs. Having advanced the research to this point, our intramural scientists entered into a collaborative agreement with Pfizer and with colleagues in academia to try to identify chemicals that would specifically block the action of JAK3 and exert immunosuppressive activity. These studies identified an agent known as CP-690,550 that does suppress the immune system. Studies to date in animal models of disease have been very promising: in the animals that had organ transplants and were treated with this new drug, none showed signs of typical, serious immunosuppressive side effects. This is probably because the mechanism of action of this new drug specifically inhibits only this particular enzyme, JAK3, and this then serves to suppress the immune system, but does not affect other cells of the body. Researchers are currently conducting additional studies in animals, and the hope is that this drug will be useful for people who have undergone organ transplantation, as well as those affected by autoimmune diseases. The story of the development of this new drug illustrates the power of translational research.
Arthritis and Other Rheumatic Diseases
Research on systemic lupus erythematosus (lupus) has resulted in tremendous scientific advances that have important clinical implications. Most recently, scientists that we supported learned that antibodies in the serum actually precede clinical findings in lupus by many years, providing one tool for physicians to identify those at highest risk for lupus and to monitor them more closely. Other researchers have identified a genetic "signature" for lupus that is present in those lupus patients who develop severe, life-threatening complications such as kidney or brain inflammation, and this finding has implications for the early diagnosis and treatment of this potentially devastating disease. We know also that lupus affects women and minorities disproportionately, and researchers have uncovered additional information on the genetic differences among various ethnic and racial groups. The hope is that understanding these genetic differences may help us to understand better how to address lupus in patients from across all ethnic and racial groups.
While we often think about arthritis and other rheumatic diseases as affecting older individuals, the fact is that these diseases have a devastating effect on children as well. Research has revealed that children with juvenile arthritis have increased anxiety, and this is associated with increased fatigue and pain frequency and intensity. This means that these children typically have reduced participation in school and social activities. The NIAMS considers research on children to be a key priority, and we will continue to pursue strategies to improve treatments as well as quality of life for children affected by chronic diseases within our mission areas.
Bone and Musculoskeletal Diseases
Osteoporosis is the most common of the bone diseases that affect Americans, and it takes an enormous toll on public health. In order to explore ways to optimize treatment of osteoporosis, the NIAMS has invested in some very important clinical trials in the study of combinations of drugs - studies that industry would not be likely to undertake. In order to build bone mass to reduce the chance of fractures, there are two primary options: the first is to slow the breakdown of bone and the second is to enhance the bone building process. The NIAMS undertook studies that combined two drugs - parathyroid hormone that builds bone and alendronate that slows bone loss. The hope was that they would work together and be even more effective than either drug alone. The results demonstrated that combination treatment was no better, and perhaps less effective, than either of the drugs alone. This has tremendous public health implications because, without this knowledge, physicians would intuitively combine these two treatments. In another study undertaken this year, researchers are testing whether a once per week dosing with parathyroid hormone is as effective as the currently recommended daily dosing regimen. Since administration of this drug is by injection, a once per week dosing option may be a more appealing option to patients. It is important that people with or at risk for osteoporosis have research-based options that will give them the maximum benefit with the fewest side effects. These latest studies provide important information to affected people and their health care providers on the treatment of osteoporosis.
As there is a clear need to develop more reliable markers of bone quality in order to predict who may be more prone to bone fracture, the NIAMS sponsored a meeting that included representatives from pharmaceutical and imaging companies as well as researchers in the bone field. The goal was to stimulate collaborations across many disciplines and thereby increase the development of novel and promising research studies as well as new technology to improve our ability to assess bone quality, and therefore fracture risk. We are hopeful that public-private partnerships will be developed in this area and that productive initiatives will be launched.
Research in the field of total joint replacements (both hip and knee) has resulted in significant progress in surgical techniques and approaches, in materials that are used to develop the joint replacements, and in understanding the importance of replacing joints that have deteriorated (due to osteoarthritis) before the deterioration is so significant that the outcome of the surgery is less successful. While joint replacements are recognized for the great success they have provided in improving public health, the field had reached a juncture where it was important to address some controversies that exist, to review the current state of the science, and to identify promising directions for future research. The NIAMS teamed with other NIH components to sponsor the Consensus Development Conference on Primary Total Knee Replacement in December of 2003. The report from this Conference not only underscored the value of knee replacements, but also provided a number of areas of research opportunity and need for the NIAMS and other NIH components to pursue in the future.
Diseases of muscle are among the most debilitating of all chronic diseases - often deteriorating quality of life and reducing length of life for affected people. Research on muscle diseases has undergone tremendous growth over the last several years. Highlights of advances include the recent report from scientists who discovered how to reverse muscle degeneration in a mouse model of Duchenne muscular dystrophy; researchers who successfully linked the gene defect in myotonic dystrophy to its biological function; the identification of a chromosomal variation in people with facioscapulohumeral muscular dystrophy; and the identification of a biochemical "switch" that directs muscle building. In addition to all of these scientific advances, the NIAMS has been actively involved in stimulating additional research and research collaborations in the muscular dystrophies. We teamed with our colleagues in the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Child Health and Human Development (NICHD) in funding three Muscular Dystrophy Cooperative Research Centers. Each Institute funds one of the three centers and, in a novel collaboration, the Muscular Dystrophy Association (MDA) provided supplemental funding to enhance research at each of these Centers. Other efforts include the work of the newly formed Muscular Dystrophy Coordinating Committee that is developing a research and education plan for muscular dystrophy, as well as the NIH Muscular Dystrophy Research Task Force that is guiding efforts to intensify research and training in this area.
Skin diseases take a tremendous toll on affected people - they can be life threatening and they have a psychological impact as well. Researchers supported by the NIAMS have made significant progress on a number of fronts related to skin diseases. Highlights include the identification of the genetic bases for predisposition to vitiligo and other autoimmune diseases. Vitiligo is an autoimmune disorder that is characterized by the loss of pigment in patches on the skin and hair. While it can affect anyone, it can be socially devastating for affected people who are more darkly pigmented. Genetic studies have localized susceptibility to vitiligo to a particular chromosomal region - the precise gene is currently being identified. Researchers expanded their studies of vitiligo and learned that other autoimmune diseases coexist with vitiligo in families, and that within the same family, there were likely to be many members with vitiligo as well as others affected by other autoimmune diseases. It is important that we understand the genetic bases as well as the triggers from the environment that may lead to the development of vitiligo and other autoimmune diseases in order to make progress in prevention and treatment. The NIAMS sponsored a meeting in September 2003 on immune modulation in the treatment of skin diseases. Recommendations from this meeting will facilitate the development of future research initiatives focused on treatment strategies for a wide range of skin diseases, including vitiligo. In addition, other researchers have made progress in our understanding of the molecular and genetic bases of psoriasis, one of the most common skin diseases and one that has a significant effect on normal daily life for affected individuals. This holds promise for improved and more targeted treatments that will minimize or eliminate the abnormal skin appearance in people with psoriasis, but have less of a detrimental effect on the immune system than many of the current therapies for psoriasis.
Melanoma is the most severe skin disease with regard to mortality, accounting for approximately half of all deaths from skin disease. Scientists are striving to understand the molecular events involved in the transformation of normal pigment cells of the skin to melanoma cells and the early progression of melanoma. A group of investigators, recognizing that certain atypical moles predisposed individuals to the development of melanoma, studied these cells in culture and added genes to turn on a particular protein (MAPK). The introduction of this activated gene resulted in the development of factors involved in melanoma invasion and metastasis, indicating that this pathway is probably important in melanoma development. This new understanding may facilitate the design of therapeutic interventions to suppress this pathway. Recognition of the molecular pathways that result in malignant transformation of melanocytes into melanoma cells and the spread of melanoma should facilitate the design of better methods for identifying the disease in its earliest stages as well as the design of better therapeutic interventions.
The NIH Roadmap for Medical Research
The NIAMS is an enthusiastic partner in all dimensions of the newly created NIH Roadmap for Medical Research. The initiatives that are being launched through the Roadmap will accelerate discoveries in areas that are critical to our mission. Of course, the people power - the cadre of researchers who will comprise the Research Teams of the Future -- is one of the most critical components of the quest to understand fundamental functions in the human body as well as what goes awry in disease. The clinical dimension of the NIH Roadmap is vitally important to our researchers and will provide much of the clinical infrastructure needed as well as enhance our ability to support greatly accelerated and more efficient clinical studies. The Roadmap initiatives in this area will provide access to the latest, state-of-the-art, and novel infrastructures, and this will mean a significant savings of investigator time as well as costs to undertake clinical research.
The most exciting and promising research advances are of limited value if they are not disseminated to patients, their families, and their health care providers. The NIAMS remains committed to a comprehensive program of information dissemination. We work closely with the many voluntary and professional groups that are concerned with diseases within our mission areas. Our goal is to both learn their needs as well as share our research findings with them. We know also that it is vitally important that information be provided to the public in ways that are culturally sensitive and accessible to the broad range of people concerned with the many chronic diseases our Institute addresses. We are very pleased to have expanded our information dissemination efforts through the newly developed NIAMS Spanish-language home page on our Institute's Web site. This site provides the latest research results and health education materials in Spanish, and it offers an opportunity for more people to learn about the mission of the NIAMS and how it is implemented through research and other initiatives to improve the health of our country.
Chronic diseases of bones, muscles, joints, and skin affect people of all ages, ethnic and racial groups, and economic strata. For people suffering from these diseases, their daily life and the quality of their life are profoundly affected. The best hope for these people remains with the proven value of medical research. Tremendous strides have been made in our fundamental understanding of normal function as well as the bases for diseases that compromise the ability of affected people to live their lives fully. We are committed to continuing to support a broad range of research studies. The support of the Administration, the Congress and the public allows us to invest in many productive areas of research. As the Director of the NIAMS, I am proud of the progress that I have had the opportunity to share with you today, and I am genuinely confident that research underway today holds great promise for the future health of the American people.