April 2018

FY 2019 Congressional Justification PDF version (209 KB)

Organization Chart

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Appropriation Language

NATIONAL INSTITUTES OF HEALTH

National Institute of Arthritis and Musculoskeletal and Skin Diseases

For carrying out section 301 and title IV of the PHS Act with respect to arthritis and musculoskeletal and skin diseases, $545,494,000.

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Amounts Available for Obligation

¹Excludes the following amounts (in thousand) for reimbursable activities carried out by this account:
FY 2017 — $3,164     FY 2018 — $3,006     FY 2019 — $2,946

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Fiscal Year 2019 Budget Graphs

History of Budget Authority and FTEs:

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Authorizing Legislation

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Appropriations History

¹ Budget Estimate to Congress includes mandatory financing.

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Justification of Budget Request

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Authorizing Legislation: Section 301 and title IV of the Public Health Service Act, as amended.

Budget Authority (BA):

 

Program funds are allocated as follows: Competitive Grants/Cooperative Agreements; Contracts; Direct Federal/Intramural and Other.

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Director’s Overview

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is the primary Federal agency responsible for supporting medical research on diseases of the bones, joints, muscles, and skin.  The diseases and conditions within the NIAMS’ mission areas touch the lives of virtually every American, impose significant financial burden, and reduce quality of life.  Recent analyses from the Centers for Disease Control and Prevention (CDC) noted that arthritis is common, disabling, and a growing major health concern. More than 54 million American adults have some form of doctor-diagnosed arthritis, such as osteoarthritis, rheumatoid arthritis, gout, and fibromyalgia, and 42.8 percent of those individuals experience activity limitations as a result of their disease.¹ Arthritis accounted for approximately $300 billion in economic burden in 2013, nearly one percent of the gross domestic product that year, and individuals with arthritis earned approximately nine percent less in wages than those who did not.² Often certain groups are disproportionately affected by diseases within the NIAMS’ portfolio. For example, recently completed population-based studies of lupus, an autoimmune disease where the body’s immune system attacks healthy tissues, confirmed that women have a higher incidence of lupus than do men.  The studies also revealed that the prevalence of lupus is greater in Hispanic and Asian Americans than in Whites, but that African Americans experience the highest prevalence.^3,4 NIAMS is working to enhance health, lengthen life, and reduce illness and disability from these and other diseases of the bones, joints, muscles, and skin. The Institute supports novel partnerships to facilitate new avenues of research, basic science studies to understand the underlying cause of disease, and translational and clinical research to improve outcomes for patients. NIAMS is also investing in the future through innovative programs designed to retain talented young scientists and clinicians in research careers.

In 2014, NIH embarked on a partnership with pharmaceutical companies and nonprofit organizations, the Accelerating Medicines Partnership (AMP), to develop new ways of identifying and validating promising biological targets for diagnostics and drug development.

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NIAMS and the National Institute of Allergy and Infectious Diseases (NIAID) are leading projects on the autoimmune conditions rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) through the AMP RA/SLE Program. One of the most exciting results of this effort is that for the first time, scientists can study the changes taking place in the affected tissues of patients at the single-cell level. This breakthrough represents a sea change in how autoimmune diseases are studied and was accomplished through the combined resources and talents of government, industry, non-profits, and academia. The synergy from this unique partnership is facilitating advances beyond those that any one of these partners could have done alone. Thus far, the program has developed standard protocols for obtaining and analyzing patient tissues and identified and validated new research tools that enable scientists to explore disease mechanisms and follow patients clinically in ways that were previously impossible. Data generated by AMP researchers is not patentable and is made freely available to the entire research community. In January 2018, AMP researchers began releasing data and results through phase 1 of the program, which compared samples from RA and SLE patients and unaffected individuals. While phase 2 of the project, to stratify patients within their disease, is ongoing, the available data resource can be leveraged by other non-AMP scientists in academic, private, and non-profit sectors to conduct their own novel studies.

Basic research is a key focus for the NIAMS. By examining the underlying biology of living systems, both in health and in disease, prevention and treatment approaches may be revealed. For example, the human body lives with a host of microorganisms, called the microbiome. It has long been understood that disease can arise when harmful microorganisms invade. Within the last decade, researchers have begun to uncover exactly what makes up a healthy microbiome, and how it may interact with an individual’s genome and other environmental exposures to cause, or protect against, disease. Atopic dermatitis, or eczema, is a common inflammatory skin disease characterized by dry patches of skin, intense itching, redness and swelling. Earlier research by NIH and others showed that individuals with eczema have a different complement of skin bacteria than those who do not. Recently, NIAMS intramural researchers expanded on that work to identify that higher levels of one particular bacteria, Staphylococcus aureus which causes staph infections, on the skin leads to development and progression of eczema. Other researchers funded by NIAMS have translated this basic understanding to develop a new therapeutic intervention, a probiotic lotion, designed to help reduce the abundance of the harmful bacteria and restore the skin microbiome to a normal state. The microbiomes of the gut and oral cavity have also been shown to be important factors in health or disease development. Using mice that model the effects of menopause in women, NIAMS-supported researchers showed that a probiotic supplement containing a specific bacterium found in some yogurt and cheese products was able to protect against bone-loss and reduce signs of inflammation. In other work, NIAMS-supported extramural and intramural researchers identified that a certain gene variant linked to a form of arthritis called ankylosing spondylitis changes the gut microbiome in animal models, and in turn induce changes in the immune system leading to inflammation and damage to joints.

NIAMS is building upon the foundation of basic research advances and translating them into novel interventions to improve health. Epidermolysis bullosa (EB) is a skin disease that causes extensive, painful blisters and skin wounds. Prior research identified the cause of a severe, inherited form of the disease, called recessive dystrophic EB (RDEB), as a faulty gene for a protein called type VII collagen. Recently, researchers conducted a phase 1 clinical trial to test a new treatment approach to aid in healing the skin of RDEB patients. In the trial, a skin biopsy was taken from RDEB patients, cultured in the lab, and then genetically modified using a harmless virus to express a normal type VII collagen. These genetically modified cells were then grown into a sheet the size of a playing card and grafted back onto the patient’s wounds to help speed healing. Three months later, 90 percent of the transferred grafts showed the type VII collagen, and a year later 50 percent of the grafts were still intact. Investigators will continue to monitor the long-term outcomes of these patients’ grafts and are building on these promising results in a phase 2 clinical trial that will enroll more patients and examine additional outcomes, such as wound pain and itch.

In order to continue making critical progress to reduce illness and disability, a robust pipeline of talented and dedicated scientists and clinicians must be cultivated. NIAMS has implemented programs to foster the development of young clinician scientists, through both in-person forums as well as tailored small grant programs and aid their transition to research independence. The Supplements to Advance Research (STAR) award program, which began in FY 2015, supports NIAMS investigators who recently renewed their first major independent award as they work to expand their research from a single, structured project into a broader, multi-faceted research program. Reflecting NIAMS’ commitment to early-career investigators, the STAR program aligns with the trans-NIH Next Generation Researchers Initiative.

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Program Descriptions and Accomplishments

Arthritis and Rheumatic Diseases: This program advances high-quality basic, translational, and clinical biomedical and biopsychosocial research to treat, cure, and prevent arthritis and autoimmune diseases. It supports the discovery and application of genetics, genomics, proteomics, immunology, and imaging insights to explain how the immune system interacts with various tissues in normal and pathological conditions. This, in turn, ensures a continuous supply of new targets on which therapies can be based. One such recent project revealed that a group of immune cells called follicular helper T cells consist of several subtypes, each of which has a distinct role in fine-tuning the immune response. While additional basic research is needed to understand how these cells regulate other parts of the immune system, the observations open up possibilities for new treatments of autoimmune diseases that are associated with overly active follicular helper T cells, and for improved vaccines that promote immune responses to protect against disease.

At the clinical end of the research continuum, NIAMS-funded investigators are conducting an open label phase II clinical trial of a drug that might enable women, whose autoimmune disease places them at increased risk of severe pregnancy complications, to deliver healthy, full-term babies. This work builds on earlier studies that defined factors that correlate with greatest risk (i.e., those women who produce an antibody known as lupus anticoagulant) and that identified the causes of the complications and an approach to prevent them (i.e., a poor blood supply to the fetus, which can be restored in mice by blocking a molecule called TNF-alpha). Other ongoing clinical projects managed by the Arthritis and Rheumatic Diseases program include several of the studies mentioned in the Patient-Reported Outcomes program portrait, and the Accelerating Medicines Partnership RA/SLE program described above.

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Musculoskeletal Biology and Diseases: This program focuses on understanding the fundamental biology of tissues that constitute the musculoskeletal system and on translating this knowledge to a variety of diseases and conditions. The portfolio covers research into causes and treatments for chronic back and neck pain, prevention and repair strategies for joint injuries or joint diseases, and the development and application of imaging tools for assessing bone quality or monitoring osteoarthritis progression. (See program portrait for an example of how long-term public-private partnerships by NIAMS are leading to the discovery of biomarkers for disease onset and progression.) Some NIAMS-funded clinical studies are addressing controversies regarding the effectiveness of common treatments for chronic musculoskeletal disorders, such as the repeated use of intra-articular steroid injections for knee osteoarthritis. This treatment is frequently prescribed for short-term pain relief, but new data show that repeated injections every 12 weeks for two years have no long-term benefit and may be associated with accelerated cartilage loss.

Other investigators are exploring tissue engineering and regenerative medicine strategies that can be incorporated into orthopaedic procedures. For example, investigators are working to develop off-the-shelf bone products that mimic or surpass the function of natural bone grafts and are readily available for spinal fusion surgeries. In one approach tested in rats, a gelatin sponge that was seeded with bone marrow or bone-forming stem cells was implanted and shown to be comparable with currently used synthetic or natural bone grafts. In other work, researchers are exploring ways to repair large regions of bone. One set of experiments in zebrafish recently revealed some of the signals that allow missing bone to regrow into its original structure. This work is an early step toward developing a comprehensive understanding of the processes to regenerate badly damaged bone. Such knowledge may one day be translated into clinical strategies to stimulate the body’s own signaling system to repair large bone defects in a way that current medical technologies cannot achieve.

Bone Biology and Diseases: This program supports a variety of projects ranging from fundamental research into the genetic and cellular mechanisms involved in the build-up and breakdown of bone in health and disease, to epidemiologic studies of lifestyle factors that can preserve bone health. Research teams are developing improved approaches to identify people who are at increased risk of fracture (see the Bone Quality Initiative example in the program portrait below) or to treat patients who have a bone disease. While osteoporosis is the most common disease in this portfolio, investigators also are exploring the molecular basis of rare bone diseases and using this information to develop potential treatments. In 2017, for example, NIAMS-funded researchers applied powerful computing technologies to results from basic bone biology studies and identified molecules that might be turned into drugs for patients who have genetic forms of rickets.

Over the past decade, bone researchers have made fundamental discoveries related to how the skeleton influences other organ systems. One group recently discovered that bone cells produce a protein that activates certain brain cells known to suppress appetite and regulate body weight and energy metabolism. While the study was completed using mice, further evidence of the biological importance of this protein comes from people with type 2 diabetes; a higher circulating level of the protein is associated with lower weight and better blood sugar control.

Looking to FY 2019, NIAMS is partnering with the National Institute on Aging and the NIH Office of Disease Prevention’s Pathways to Prevention Program on a workshop that will clarify major questions related to the safe, long-term use of bone-building or bone-preserving drugs and will identify evidence gaps and areas of future research. Drugs such as bisphosphonates prevent fractures in older people who have osteoporosis. However, many people are reluctant to use them because of concerns about rare but serious side effects. Some experts consider the increase in under-diagnosis and under-treatment of osteoporosis to be the harbinger of a public health crisis.

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Muscle Biology and Diseases: This program’s overarching objective is to explain muscle’s role in health and, ultimately, to treat or prevent skeletal muscle diseases and disorders such as muscle ion channel diseases, inflammatory myopathies, disuse atrophy, skeletal muscle injury, and loss of muscle mass and strength associated with aging and diseases. For example, investigators are studying the molecules that control how much calcium is available to regulate muscle contractions. Using mice, they determined that calcium accumulation inside muscle cells causes damage that mimics what is seen in people who have a disease called malignant hyperthermia. They then successfully treated the animals with a drug that is FDA-approved for conditions that are associated with similar cell stress responses.

Pompe disease is an inherited condition where individuals lack an enzyme to metabolize the sugar glycogen, and as a result, glycogen builds up in the muscles. If not detected early in babies with the condition, their muscles do not develop properly. Without treatment to replace the missing enzyme, heart and breathing problems and even death can occur. After decades of work, a group of investigators developed a gene-transfer approach that, when recently tested in mice, shows promise for treating this rare condition. While the study’s main goal was to determine if immune reactions to the current enzyme replacement therapy given to patients could be prevented, it also demonstrated that the technique could potentially replace the existing treatment. These results directly contributed to an FDA-approved clinical trial that NIAMS began funding in FY 2017.

While the examples mentioned above may lead to new treatments, other NIAMS-funded studies may lead to improvements in how existing therapies are prescribed. Researchers examined cell culture and mouse models to understand how glucocorticoids preserve muscle function in boys who have Duchenne muscular dystrophy. They found that weekly dosing increases the level of two genes involved in muscle cell membrane repair, while daily dosing activates cell pathways that cause muscle to shrink and weaken. If the responses also occur in patients, this study could directly inform prescription instructions that would maximize the drugs’ therapeutic benefit while minimizing negative side-effects. This work could also extend beyond the muscular dystrophies, as approximately one percent of the entire U.S. population is treated chronically with glucocorticoids for other conditions.

Skin Biology and Diseases: This program’s support for basic, translational, and clinical research includes work on the developmental and molecular biology of skin, the skin as an immune organ, and the genetics of skin diseases. Investigators studying the causes of ectodermal dysplasias – a family of disorders where skin, hair, nails, sweat glands, taste buds, and teeth develop or function incorrectly – recently identified some of the molecules that are involved in the condition’s more debilitating symptoms. This linkage of patients’ genetic defects to specific disease manifestations suggests that known compounds which alter the pathways involved may be an effective treatment for preventing or healing the overgrown, painful cracks that develop on patients’ palms and soles.

Wound healing is another key component of this portfolio. NIAMS-funded investigators recently discovered that cells involved in recovery from deep cuts—which often involves scaring—can also become fat cells that underlie healthy skin tissue. Although little is known about how to direct skin repair toward regenerating normal skin instead of scaring, hair follicles may hold a clue because they seem to be a pre-requisite for the formation of these new fat cells. This and related findings are opening new avenues of research which could lead to novel treatment strategies for severe scaring and fibrotic diseases.

Itch, like wound healing, is a common condition that falls under this program. Scratching in response to an itch is a contagious behavior in mice as well as in people. Recent research into the brain changes that occur when one mouse sees another scratching has uncovered a neurotransmitter that is responsible for contagious itch. Although it is too early to tell what the immediate impact of the findings will be, the discovery opens the possibility of novel interventions to treat chronic itch that target the brain directly.

Intramural Research Program (IRP): NIAMS’ IRP conducts innovative basic, translational, and clinical research relevant to the NIAMS mission and trains investigators who are interested in related careers. Its basic and physician scientists study the genetics, etiology, pathogenesis, and treatment of rheumatic, autoimmune, inflammatory, bone, skin, and muscle diseases. Foundational research by NIAMS intramural scientists on immune cells and how they communicate with each other led to the discovery of the JAK-STAT signaling pathway and formed the scientific basis for development of a new class of drugs, called Jakinibs. Some Jakinibs have been FDA-approved for the treatment of RA and certain cancers. Recently, NIAMS intramural investigators examined if one of these drugs – tofacitinib, which is approved for treatment of RA – could alleviate disease symptoms in a mouse model of lupus. Based on positive findings in mice, NIAMS clinicians have initiated a phase 1b clinical trial to determine the safety and tolerability of tofacitinib for SLE patients with active disease. The program portrait below highlights additional work being pursued in the NIAMS IRP to understand how autoimmune diseases develop.

In FY 2018, the Dermatology Branch joined the NIAMS IRP, transitioning from the National Cancer Institute intramural program. This addition provides a great opportunity for synergy across the scientific programs within NIAMS, as well as between NIAMS and many others across the NIH. The Dermatology Branch conducts basic and clinical investigations of skin biology and researches the causes, diagnosis, and treatment of skin disease. Research interests include the development and maintenance of normal skin and changes that occur in skin cancer; understanding interactions between skin and the microbiome; and immune cell function in the skin. In addition, the Branch supports the Dermatology Consultation Service in the NIH Clinical Center, one of the busiest clinical services at the research hospital and is responsible for all outpatient and inpatient dermatologic patient care.

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Research Management and Support (RMS): The RMS budget supports the scientific, administrative management, and information technology activities associated with the NIAMS’ day-to-day operations. In FY 2017, NIAMS managed more than 1,178 research grants and centers, as well as 37 research and development contracts and 298 individual and institutional full-time research training positions. NIAMS supported 550 clinical research studies, including 63 clinical trials.

NIAMS launched a redesigned website in FY 2017, in alignment with its mission of supporting information dissemination. The site, which is hosted in the cloud, is built with an open source content management system that promotes streamlined workflow processes and rapid content updating. The website can be displayed across multiple screen sizes, including mobile devices, and provides anytime-anywhere access to information and resources, including a searchable funding database, training opportunities, and health information. The website features a new Community Outreach portal that was designed to empower organizations and community leaders that reach diverse, underserved populations with health education tools. In addition, a large multi-lingual collection of information and resources is available and can be tailored to audiences at local levels. Together, these platforms provide NIAMS with a range of complementary outreach strategies to share research results and provide evidence-based health information to reduce disease burden across diverse populations.

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Details of Full-Time Equivalent Employment (FTE)

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Detail of Positions

¹ Includes FTEs whose payroll obligations are supported by the NIH Common Fund.

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