Statement for the Record
Senate Subcommittee on Labor-HHS-Education Appropriations

April 2, 2014

Stephen I. Katz, M.D., Ph.D., Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
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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) of the National Institutes of Health (NIH). The fiscal year (FY) 2015 NIAMS budget of $520.189 million includes an increase of $0.851 million over the comparable FY 2014 level of $519.338 million.

The NIAMS supports a broad range of research, training, and information dissemination activities. Many of the conditions within the NIAMS mission are very common while some are rare, affecting only a few thousand people world-wide. All have a major impact on the quality of people’s lives. Diseases addressed by NIAMS affect individuals of all ages and of all racial and ethnic backgrounds; many disproportionately affect women and minorities. Over the years, NIAMS-funded research teams have made significant progress in uncovering the causes of and improving the treatments for many disorders of the bones, muscles, joints, and skin.

While many treatments for arthritis and musculoskeletal and skin conditions have their origins in NIH-supported basic research, the timeframes for translating fundamental knowledge into therapies remain unacceptably long, and too many potential therapies fail late in development. To improve the drug development process, NIAMS has partnered with industry, non-profit groups, and other government agencies for the NIH Accelerating Medicines Partnership program in lupus and rheumatoid arthritis (RA). Through the program, a network of investigators will use advanced tools and techniques to analyze blood and tissue samples from patients. The overall goals are to gain insights into lupus and RA biology, improve the selection of biological targets for drug development, and ultimately produce new therapies.

The advent of technologies for collecting and analyzing large amounts of data corresponds with an increasing appreciation of the interactions that occur among different tissues and organ systems, and with the microorganisms inside our body or on our skin. When researchers compared the gut microbes of people who had newly diagnosed, untreated RA with those found in the digestive tracts of healthy people, patients with RA who were receiving treatment, and psoriatic arthritis patients, they found that the bacterium Prevotella copri (P. copri) was more abundant in patients with new-onset RA than in the other groups. If additional studies determine that altered levels of P. copri contribute to RA, therapies that target the bacterium could help to prevent the disease or delay its onset. Similarly, another group of researchers recently demonstrated that Staphylococcus aureus colonies on the skin of people who have atopic dermatitis, or eczema, release a toxin that causes skin inflammation. This finding provides an impetus for further studies into whether blocking the toxin could help people who are susceptible to atopic dermatitis.

Other research is uncovering complex connections between the immune system and skeletal health, and the role of hormones produced by bone on the development and function of the nervous system. Recent findings have linked the misfolding of a protein that helps immune cells recognize and destroy invading bacteria or viruses to the bone erosion that characterizes spondyloarthritis of the spine. Other research has revealed that the bone-derived hormone osteocalcin is capable of interacting with neurons in the brain and influencing brain structure and behavior, at least in mice.

Many people think of broken bones as a normal part of an active, healthy childhood. Although any bone will break if enough force is applied to it, researchers are learning that the bones of some children and teens have structural deficits that can be readily identified based on what the patient was doing when the bone was broken. Children who broke an arm because of moderate impact, as would occur when falling off a bicycle, had bones that resembled their uninjured peers; but, those whose forearm bones broke upon mild impact (e.g., a fall during a minor playground scuffle) showed signs of compromised bone strength and bone quality. While we do not know the extent to which bone weakness during childhood predisposes people to osteoporosis and fragility fractures later in life, this study is the first to suggest that a simple screening question could identify the young people who might benefit most from dietary changes and activities to improve bone health.

NIAMS also is involved in efforts to identify laboratory-based or imaging biomarkers that will guide treatment development or will improve patient care. Activities include the Foundation for the NIH (FNIH) Biomarkers Consortium project to evaluate biochemical and imaging biomarkers for more precise ways of measuring osteoarthritis progression during clinical trials; this project builds on resources created by the Osteoarthritis Initiative (OAI), a public-private partnership spearheaded by NIAMS and the National Institute on Aging with support from other NIH components, the U.S. Food and Drug Administration, the FNIH, and private sponsors. A separate research team, focused on molecular changes associated with scleroderma, recently reported that blood levels of a protein appeared to distinguish between patients who were likely to develop life-threatening lung complications that require aggressive treatments and those whose disease would not warrant risky therapies. Investigators are confirming their observations as a next step before the findings are applied clinically.

Additional research into disease-associated genetic defects and molecular pathways is pointing to new uses for drugs that have been approved for other conditions. Work by investigators studying a group of muscle diseases called the disferlinopathies—which includes limb-girdle muscular dystrophy type 2B—suggests that calcium channel blocking drugs might reduce some of the tissue damage that accumulates as the diseases progress. Another example comes from a team that identified 42 areas in the human genome that are associated with RA; many of the gene products are already targeted by existing drugs. These potential drug repurposing opportunities will be explored more thoroughly before clinical trials can begin in patients.

Once results from clinical studies are available, many health care providers insist that findings be validated before changing how they practice medicine. The ability to verify conclusions is equally important at the basic and preclinical levels of research, particularly when results become the basis for clinical trials. In FY 2015, NIAMS plans to refocus the Pilot and Feasibility Clinical Research Grants in Arthritis and Musculoskeletal and Skin Diseases program—a grant mechanism to foster early-stage clinical trials on which larger, more robust studies will be based—to emphasize the need for a strong scientific premise on which a proposed project is based.

The NIAMS is committed to ensuring that well-trained basic scientists and clinical researchers are prepared to conduct cutting-edge studies related to rheumatic, musculoskeletal, and skin diseases. The Institute awards a combination of institutional training grants and individual fellowships for this purpose. NIAMS has expanded its participation in NIH training programs for FY 2015 to include the Ruth L. Kirschstein National Research Service Awards for Individual Predoctoral MD/PhD and Other Dual Doctoral Degree Fellows (F30) program. The Institute also has begun meeting with clinical or patient-oriented research career development awardees—both early in their award and as they are about to transition to independent careers—to identify challenges that they face and ways to better support them and future awardees.

As part of a commitment to communicating about NIAMS programs and research results, NIAMS has enhanced its outreach to patients, health care and research professionals, and the general public via social media and other activities. Building on a successful 2013 effort to ensure that the results of NIH research investments and health messages reach all Americans, NIAMS again partnered with other components of the Department of Health and Human Services and with patient advocacy groups to create a new set of health planners, titled A Year of Health, A Guide to a Healthy 2014 for You and Your Family. In the past two years, NIAMS received requests for these health planners from all 50 states and five U.S. territories, demonstrating a robust need for credible, research-based health information in African American, American Indian/Alaska Native/Native Hawaiian, Asian American/Pacific Islander, and Hispanic/Latino communities.

Looking to the future, we are updating the Institute’s Long-Range Plan. As with the FY 2010-2014 plan, the new document will inform the Institute’s priority setting process while enabling the NIAMS to adapt to the rapidly changing biomedical and behavioral science landscapes. When complete, the plan will outline the Institute’s perspective on research needs and opportunities within the NIAMS mission, and will serve as a resource for all who are interested in our activities.