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Statement to the House and Senate Appropriations Subcommittees
April 6, 2006 (historical)
Stephen I. Katz, M.D., Ph.D., Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Mr. Richard Turman, Deputy Assistant Secretary, Budget
Mr. Chairman and Members of the Committee:
I am pleased to present the Fiscal Year (FY) 2007 President's budget request for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The FY 2007 budget includes $504,533,000, a decrease of $3,399,000 below the FY 2006 enacted level of $507,932,000.
The NIAMS was created by an Act of Congress nearly 20 years ago, and since its inception, the Institute has contributed to significant research progress in areas of public health importance across diseases that are common, costly, and have a major impact on quality of life, disability, and mortality. Research milestones in the history of the Institute include the development of life-saving treatments for kidney failure in patients with lupus, and ground-breaking work to uncover the genetic bases of periodic fever syndromes that affect both children and adults, among many others.
Most recently, investments that NIAMS made as a result of the NIH budget doubling are bringing results that will directly benefit patients. These include support for large-scale clinical trials in areas of high public health impact, such as osteoporosis and back pain; efforts in biomarkers research and epidemiology studies for common conditions such as osteoarthritis, as well as uncommon, but often devastating, disorders such as scleroderma; and new initiatives in translational research for diseases such as muscular dystrophy. Looking to the future, NIAMS will continue its commitment to fund outstanding science across a broad spectrum to enable us to better understand, treat, and, ultimately, prevent diseases of the bones, joints, muscles, and skin.
The NIAMS has made significant investments in studies to identify risk factors and biomarkers of disease, in an effort to facilitate the early identification of signs and symptoms, and to develop interventions that are more effective. This is particularly important from a public health perspective for common conditions such as osteoporosis and osteoarthritis that already afflict tens of millions of Americans, and will affect even more as the U.S. population ages in the coming decades.
In the area of osteoporosis, the NIAMS, along with the National Institute on Aging, has provided steady support for the Study of Osteoporotic Fractures (SOF), a multi-site clinical investigation to determine the risk factors for osteoporotic fractures in older women. Begun in 1986, SOF scientists recruited 9,704 white women aged 65 and older from 4 metropolitan areas for this study. In 1997, an additional 662 African American women who are now seen with the original cohort were enrolled. Major contributions from this long-term study include the findings that bone mineral density (BMD) of the hip is the best predictor of all types of fractures, and that weight loss and parental history of hip fractures are among the most important risk factors for this condition. SOF investigators have also learned that the relationship of BMD and fracture risk is similar in white and African American women, but that at every level of BMD, fracture rates are 30 to 40% lower in African American women. These insights are providing clinicians with important information about which women are at most risk for this debilitating disease, so that prevention strategies may be used more effectively. Similar epidemiological studies have now been launched to learn about risk factors for osteoporosis in men.
With respect to osteoarthritis, the NIAMS partnered with the National Institute on Aging, several other NIH components, and four pharmaceutical companies in establishing the Osteoarthritis Initiative, a public-private partnership aimed at developing clinical research resources that support the discovery and evaluation of biomarkers and surrogate endpoints for osteoarthritis clinical trials. For the first time, a public-private partnership is bringing together new resources and commitments to help find biological markers for the onset and progression of osteoarthritis. Recruitment of participants is actively underway, and by the end of FY 2005, more than 3,800 participants have been recruited. One year follow-up measurements have been carried out on over 1,000 participants, and will continue for the next 4 years. All data and images collected will be available to researchers worldwide to help quicken the pace of scientific studies and biomarker identification. This consortium serves as a model for future endeavors that link the public and private sectors.
The NIAMS is taking full advantage of the explosion of information related to genetics, genomics, and proteomics to pursue the causes of complex diseases, and how best to treat them. This includes recent work which identified a genetic variation that doubles the risk of developing rheumatoid arthritis. Scientists have long suspected that autoimmune diseases such as rheumatoid arthritis result from a combination of genetic and environmental factors. Now, a NIAMS-funded research team has identified a specific genetic variation, called a single nucleotide polymorphism or SNP, that increases rheumatoid arthritis risk twofold. The SNP is located within a gene that codes for a particular enzyme that is known to be involved in controlling the activation of white blood cells, called T cells, that play an important role in the body's immune system. Under normal conditions, the enzyme works as a negative regulator: it inactivates a specific signaling molecule which, in turn, interrupts the communications and keeps immune cells from becoming overactive. However, in cases where the SNP is present in one or both copies of a person's genes for this enzyme, the team found that the negative regulation by the enzyme appears to be inefficient, allowing T cells and other immune cells to respond too vigorously, causing increased inflammation and tissue damage. The implications of this finding go beyond a better understanding of rheumatoid arthritis risk. It may also help explain why different autoimmune diseases tend to run in families, since this gene variant is also found in diabetes and lupus.
In other efforts, researchers have recently made breakthroughs in understanding the genetics underlying psoriasis, a chronic skin disease characterized by scaling and inflammation. This disorder occurs when skin cells rapidly pass from their origin below the surface of the skin and pile up on the surface before they have a chance to mature. Usually this movement (also called turnover) takes about a month, but in psoriasis it may occur in only a few days. Recent studies funded by the NIAMS are helping scientists and doctors to understand the disease process at the molecular level, and what role genes play in predisposing people toward psoriasis. In one such project, researchers investigated the role of both genes and the environment in psoriasis, psoriatic arthritis, and atopic dermatitis, another inflammatory skin condition.
The researchers found similarities in genetic susceptibility for psoriasis and atopic dermatitis. As for psoriatic arthritis - a condition in which inflamed joints produce symptoms of arthritis for patients who have or will develop psoriasis - they found that the presence of modifier genes can indicate which people with psoriasis are also at risk for psoriatic arthritis.
A key ingredient in research success is translation: work to bring insights from the laboratory bench to the patient bedside, and back again, with the ultimate goal of improving patient care and public health.
In this vein, NIAMS has recently launched a new program to bring together basic and clinical scientists in a targeted and organized way. The Centers of Research Translation (CORT) program emphasizes the translation of results from basic to clinical studies, as well as translating findings from clinical research to enhance and focus the approaches used in basic studies - all with the goal of improving public health.
This commitment to translational research is bringing results in many areas, including the field of muscular dystrophy research. NIAMS supports two of the six Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers: the first, at the University of Pittsburgh, focuses on gene and stem cell therapies to treat muscle disease; and the second, located at the University of Pennsylvania, is examining strategies to inhibit muscle degeneration and promote muscle growth. These centers promote side-by-side basic, translational, and clinical research; provide resources that can be used by the national muscular dystrophy and neuromuscular communities; and provide training and advice about muscle diseases for researchers and clinicians.
The Institute has also launched new initiatives to encourage translational research in all forms of muscular dystrophy, and to stimulate career development opportunities for muscle disease researchers. These efforts are designed to facilitate the development of new and more effective treatments for muscular dystrophy, and to increase the number and quality of investigators in basic, translational, and clinical research focused on this disease.
Regenerative medicine - a multidisciplinary field that involves the life, physical, and engineering sciences - is an emerging area of research that cuts across several NIAMS programs. For example, important advances have been made recently in the development of promising new polymers for cartilage repair. Cartilage is a tissue that lacks capacity for self-repair. However, multidisciplinary studies by biologists, engineers, physicians, and other are providing new strategies for treating degenerative cartilage that may result in treatments for articular cartilage lesions. Researchers funded by the NIAMS have developed a class of injectable materials based on a biodegradable polymer, OPF (oligo-polyethylene glycol fumarate), for cartilage tissue engineering. Short-term studies in experimental animals demonstrated excellent tissue filling and integration resulting from implantation of these materials into cartilage defects. The polymers were also designed to deliver bioactive molecules (such as growth factors) as well as cells (such as chondrocytes or progenitor cells) to cartilage lesions to enhance tissue repair. Early results show that chondrocytes remain viable, proliferate, and synthesize cartilage matrix components in these polymer gels. Taken together, these results indicate that OPF gels are promising materials for cell delivery in cartilage repair strategies.
The scientific advances and innovative initiatives highlighted above paint a picture of research progress that has benefited millions of American children and adults. In the coming fiscal years, NIAMS will focus on strategic collaborations by building partnerships to pursue shared goals across public, academic, and private research entities. A primary example of such a coordinated effort is the Collaborative Initiative on Bone Strength. NIAMS - in conjunction with other NIH components, the Food and Drug Administration, and industry partners - is exploring a potential public-private collaboration on bone strength. The main goals of such an initiative would be to provide data supporting the use of new bone strength markers as surrogate endpoints for fractures in clinical trials, and to find measurements that predict risk of fracture more accurately than does bone density. This would facilitate the continued development and approval of new treatment alternatives to prevent fractures through the support of clinical trials that are smaller, shorter, and less expensive than current studies.
Finally, NIAMS is placing a high priority on strengthening the pipeline of well-trained investigators across the Institute's areas of research interest. This commitment includes funding for the new NIH award program, "Pathway to Independence," to support young investigators, as well as an enhanced emphasis on basic, translational, and clinical training at the major research centers supported by NIAMS. All of these activities are driven by our dedication to fulfill the mandate that Congress gave the Institute when it created NIAMS; namely, to reduce the burden of illness and to enrich the quality of life for all Americans affected by diseases within our mission.