Statement to the House Appropriations Subcommittee
April 28, 2010 (historical)
Stephen I. Katz, M.D., Ph.D., Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Mr. Chairman and Members of the Committee:
I am pleased to present the President’s Fiscal Year 2011 Budget for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH). The FY 2011 budget includes $555,715,000, which is $16,861,000 more than the comparable FY 2010 appropriation of $538,854,000.
As the primary Federal agency for supporting medical research on diseases of the bones, joints, muscles, and skin, NIAMS touches the lives of nearly every American. Its impact and importance are expanding as the population ages in the United States, and around the globe. The World Health Organization (WHO) estimates that osteoporosis (a disease characterized by low bone mass that commonly occurs with aging) causes more than 8.9 million fractures annually worldwide. It projects that the disease’s prevalence will increase by more than 3-fold in the next fifty years. However, decades of NIH research helped to create new treatment and prevention strategies to reduce the burden osteoporosis fractures and related bone diseases place on individuals, their families, and society.
NIAMS-funded research also contributed to development and testing of other treatments, including biologic therapies for autoimmune and rheumatic diseases. Now, under the American Recovery and Reinvestment Act (ARRA) of 2009, investigators are creating tools and collecting data to determine which therapies are most appropriate for different types of individuals who have joint pain due to rheumatoid arthritis. As knowledge becomes available, researchers will be able to develop evidence-based algorithms that community-based rheumatologists can use to customize their patients’ care.
Since its inception, NIAMS has encouraged the pursuit of fundamental discoveries, the translation of basic science findings into treatments, and the study of existing therapies to ensure that patients benefit from the best available interventions. In FY 2011, the Institute will maintain this approach, while continuing to investigate research opportunities that could reduce the disability and health care costs associated with arthritis and musculoskeletal and skin conditions.
Applying State-of-the-Art Research Approaches to Understand Biology and Disease
While many recent advances have come from conventional research methods, an increasing number of investigators are integrating new imaging, tissue-engineering, and gene-sequencing resources into their studies. Over the past decade, technical progress has facilitated very large studies that allow researchers to identify the constellation of genetic changes that lead to, or protect against, complex diseases within the NIAMS mission. Such information reveals new drug targets, but also can have more immediate applications for people who already have developed a disease. Last summer, researchers found genetic markers that give people who have an inflammatory spine disease, ankylosing spondylitis, insight into how severe their disease is likely to become—knowledge that may motivate them to follow their treatment plans.
To speed identification of genetic changes that influence disease susceptibility or severity in other conditions—such as osteoarthritis, osteoporosis, lupus erythematosus, and psoriasis—NIAMS-supported scientists are analyzing resources from investments in population-based studies and will make the data available to all researchers. For FY 2011, NIAMS is encouraging follow-up, fine-mapping analyses that researchers sometimes need before they can translate genome-wide-association data into clinical applications.
While some investigators are identifying gene sequences associated with disease, others are studying changes in gene activity that control how and when cells specialize, how cells communicate these changes as they reproduce, and how the messages vary with age. With techniques that emerged during the past three years, researchers converted cells donated by facioscapulohumeral muscular dystrophy patients back into stem cells; now they are exploring disease mechanisms and possible therapies with NIAMS support. Other NIAMS researchers recently identified molecules that allow embryonic stem cells to develop into muscle. This discovery is important because, if scientists can control cell and tissue development, stem cells may be used to model diseases and test therapies. Likewise, the ability to harness a recent discovery about how immune cells adapt to different environments could change the treatments available to people who have autoimmune or infectious diseases. These findings come from a new area of research called epigenomics, which examines instructions about gene expression that cells relay to their progeny during cell division. For FY 2011, NIAMS is encouraging additional epigenomic research in its mission areas.
Translating Discoveries into Treatments
When symptoms and disease course vary widely among patients, as they do with autoimmune diseases such as rheumatoid arthritis and lupus, physicians can have difficulty making diagnoses and determining which interventions are best for an individual. Therefore, many NIAMS investigators are characterizing biomarkers (molecules, structural characteristics, or genetic sequences) that offer insights into a person’s disease risk, the disease’s characteristics, and the patient’s response to a given treatment. For example, researchers are testing whether immune system molecules may help with early diagnosis of rheumatoid arthritis and predict disease severity. They hope to integrate the markers into a new test to enable patients to start disease-modifying treatments before irreversible tissue damage occurs.
Biomarkers research also is bearing fruit in other areas. Scientists have discovered gene expression differences that could lead to better ways to classify, predict outcome, and treat juvenile idiopathic arthritis (JIA). The findings take pediatric rheumatologists a step closer to classifying JIA more precisely, and to developing individually tailored treatments that maximize benefits, while minimizing risks, for the nearly 300,000 American children that the National Arthritis Data Workgroup estimates have JIA.
Although usually associated with wear-and-tear due to advancing age, young people also can develop osteoarthritis. Often, it occurs following a joint injury that does not heal properly. Although tears to the anterior cruciate ligament (ACL) during sports activities can be repaired, operations do not restore a knee to its pre-injured state. NIAMS-supported scientists developed a new surgical technique that improves initial ACL healing in animals, and are collecting additional, longer-term data in preparation for a clinical trial to test whether the procedure restores function and lessens future osteoarthritis risk in patients. Other NIAMS activities to reduce the burden arthritis places on society entail partnerships within and beyond the NIH. The Institute recently renewed its support for the Osteoarthritis Initiative—a public-private partnership to help identify imaging and molecular biomarkers of osteoarthritis—through FY 2014.
Finding and Testing Therapies Through Clinical Research
Leading an international team of investigators, NIAMS researchers recently discovered a new autoinflammatory syndrome, a rare genetic condition that affects children shortly after birth. The scientists termed the new syndrome DIRA (deficiency of the interleukin-1 receptor antagonist). They successfully treated patients with an existing drug, anakinra, which the U.S. Food and Drug Administration originally approved for people who have rheumatoid arthritis. Future work will build off of this discovery and should lead to early diagnosis of DIRA patients and to initiation of life-saving treatment. Although mutations that cause DIRA are rare, screening programs may be worthwhile in certain regions of the world. As many as 2.5 percent of the population of northwest Puerto Rico carry the mutation, which also may be more common in individuals of Dutch descent.
As part of NIAMS’ commitment to put science to work for the benefit of health care reform, NIAMS-funded researchers are partnering with a nationwide alliance of pediatric rheumatologists to help children who have autoimmune diseases. With funding through ARRA, they have established a framework that they can use to conduct comparative effectiveness research and to accelerate subsequent clinical studies of potential treatments. The Institute also is enhancing its clinical research portfolio in other disease areas. It is encouraging the development of tools that clinical researchers can integrate into patient studies and assess not only whether an intervention alters a disease process, but also its effects on patients’ physical, mental, and social well-being.
Although NIAMS-supported research has improved the lives of many who suffer from arthritis or musculoskeletal or skin diseases, a goal for FY 2011 is to spread these benefits to even more people. As part of its outreach efforts, NIAMS integrates scientific findings into health information for patients, health-care providers, and the public. NIAMS delivers research results and health information to diverse populations through activities that include its National Multicultural Outreach Initiative, an effort to improve the health and healthcare of ethnic and minority populations.
Recognizing the continued need for scientists who can conduct clinical research and non-clinical researchers who are well-versed in multiple disciplines, NIAMS recently sharpened the focus of its Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (T32) Programs to emphasize these areas. Also in FY 2010, NIAMS expanded its Building Interdisciplinary Research Teams initiative to further encourage established scientists to partner with investigators outside of their disciplines. Plans for FY 2011 include evaluating the program’s effectiveness.
To heighten awareness about research opportunities within the NIAMS mission, the Institute released an update of its long-range plan for FY 2010-2014. The plan, which reflects input from the scientific and lay communities, describes opportunities in the Institute’s key areas of programmatic emphasis. It also highlights topics that transcend all research endeavors and require attention to ensure that NIAMS activities benefit the broadest possible cross-section of Americans today, and continue to do so tomorrow.