FY 2019 Annual Statement to the Appropriations Committee
Mr. Chairman and Members of the Committee: I am pleased to present the President’s Fiscal Year (FY) 2019 budget request for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH).
NIAMS RESEARCH IMPACTS EVERYONE
NIAMS is the primary Federal agency for supporting medical research on diseases of the bones, joints, muscles, and skin. As such, our work touches the lives of nearly every American. A 2018 publication by the Centers for Disease Control and Prevention notes that an estimated 23 percent (54 million) of Americans have been diagnosed with some form of arthritis, including osteoarthritis, rheumatoid arthritis, gout, and fibromyalgia; 24 million of whom have symptoms severe enough to hinder activities they want or need to do. This problem is expected to grow as our population ages; 78.4 million adults will have arthritis by 2040 if current trends continue. When arthritis is combined with other bone and joint conditions such as neck and low back pain, osteoporosis, and musculoskeletal injuries, the total cost of medical care and lost wages is estimated to be $874 billion annually. Diseases in the NIAMS research portfolio also have a global impact. In 2015, low back and neck pain was the leading cause of disability worldwide, while skin diseases such as eczema and psoriasis ranked fifth.
NIAMS is enhancing health, lengthening life, and reducing illness and disability by supporting basic and translational research and clinical trials that will inform medical practice; training the next generation of bone, joint, muscle, and skin scientists; and disseminating health information and the findings from the studies it supports to all Americans. For the remainder of my statement, I will describe a few of the many recent research activities that are benefiting people today and enabling future advances.
RESEARCH ADVANCES FUNDED BY NIAMS
My first two examples focus on the risks and benefits of steroids, which an estimated one percent of the entire U.S. population takes as chronic therapy. A team of researchers studying the effects of repeated steroid injections for knee pain found that people who received shots every twelve weeks for two years showed worsening joint damage and no long-term reduction in pain compared with those who received saline injections. While this study did not evaluate the benefits of steroid injections into the knee for short-term pain relief, it does not support their long-term use for treatment of symptomatic knee osteoarthritis. Another group of investigators looked at the mechanisms by which steroids preserve muscle function for boys who have Duchenne muscular dystrophy. Using cells and a mouse model, the team determined that a weekly dosing regimen increases the activity of two genes involved in muscle cell repair, while daily dosing activates pathways that cause muscle to shrink and weaken. Their discovery explains the seemingly contradictory results of previous studies into the drugs’ effects. If these observations from cell cultures and mice also occur in patients, this study could directly inform how steroids are prescribed to maximize their therapeutic benefits while minimizing their negative effects.
After decades of investigating Pompe disease, a rare, life-threatening condition that cripples the muscles, NIAMS-funded researchers have developed a gene-transfer approach that shows promise in mice. While the study’s main goal was to test whether the strategy would prevent the animals from developing an immune response, it also demonstrated that this gene therapy could potentially replace standard care. These results directly contributed to an investigational new drug approval by the Food and Drug Administration to move this approach into clinical trials. Gene therapy also holds promise for people who have the rare and life-threatening skin disease recessive dystrophic epidermolysis bullosa, which causes fragile, blistering skin. In a phase 1 clinical trial, investigators collected skin biopsies from four patients and used a harmless virus to correct the gene for the defective skin protein in the patients’ cells. Next, they coaxed the genetically modified cells to grow into sheets of skin about the size of a deck of playing cards. Then, the new skin was grafted back onto patients to speed healing of the open wounds that characterize the disease. After 12 months, half of the two-dozen grafts were still covering patients’ wounds. Investigators will continue monitoring these patients and are recruiting people for a phase 2 clinical trial.
NIAMS research is also developing techniques to help clinicians identify which patients are likely to have more severe or rapidly progressing disease. For example, researchers found that positron emission tomography (PET), a technique that can visualize the body’s metabolic processes, could be used to distinguish between patients who have large vessel vasculitis or other diseases with similar symptoms. PET may also help clinicians predict which patients are at highest risk of disease relapse. Another study examined children with juvenile myositis, a disease where the muscles are attacked by antibodies in the patients’ blood. The investigators found that children with a certain type of antibody experience worse muscle disease and more severe weakness. This finding also explains why these children show less benefit from existing therapies and opens a possibility for better treatments. Other researchers discovered blood markers that may distinguish the subset of people who have systemic sclerosis that are at risk of developing interstitial lung disease (the leading cause of death for these patients). This advance also may lead to new therapies.
Other studies of basic cellular processes hold promise for people who suffer from skin diseases. Investigators determined that a molecular pathway involving the protein JAK1 is involved in chronic itch. They then tested whether an existing drug that blocks JAK signaling could help people who do not respond to other treatments (e.g., some cases of atopic dermatitis). Their results were promising although further clinical studies are needed to confirm the findings. Additional teams of researchers are examining how microbes on the skin may influence a person’s susceptibility to atopic dermatitis. A pair of studies, focusing on the role of the bacterium Staphylococcus aureus in driving the disorder, suggest that reducing S. aureus by increasing beneficial skin bacteria could be an effective treatment.
NIAMS-funded research is also having an impact beyond arthritis and musculoskeletal and skin diseases. For example, psoriasis has been linked to an increased risk of developing type 2 diabetes. A new finding that the risk of diabetes is highest for those with the most severe psoriasis sheds light on the causes of both diseases and provides compelling evidence that certain patients should receive targeted diabetes prevention strategies. Other investigators are showing that while early antiretroviral therapy saves HIV patients’ lives, it also damages their bones, emphasizing the importance of developing bone-preserving strategies for this population. Weight loss due to bariatric surgery, another life-saving intervention, also is associated with bone loss, and researchers are beginning to understand the role that glucose metabolism plays in bone health. This discovery could lead to targeted prevention and treatment strategies for osteoporosis, the skeletal complications of bariatric surgery, and diabetic bone fragility. Still other research is explaining why muscle breaks down in cancer patients (a process known as cachexia). A number of molecular pathways and targets underlying the muscle wasting process have been discovered recently, and investigators are beginning to identify existing drugs or new targets to stop this from occurring.
LOOKING TO A PROMISING FUTURE
The wide reach of NIAMS-funded research is allowing people affected by diseases within our mission to benefit from large multi-agency programs such as the Cancer Moonshot Program and the Regenerative Medicine Innovation Project supported by the 21st Century Cures Act. Moving forward, investigators will examine connections between immunotherapies for cancer and autoimmune disease and will continue to be encouraged to apply for funding for research on bone, joint, muscle, and skin regeneration. NIAMS, along with the National Institute of Allergy and Infectious Diseases, continues to lead the Accelerating Medicines Partnership (AMP) in rheumatoid arthritis and lupus which is working to identify and validate promising biological targets for those diseases. With guidance from NIAMS, three other Institutes, and the NIH Common Fund, the trans-NIH Molecular Transducers of Physical Activity in Humans program continues to make progress developing a database that researchers can use to elucidate changes that take place in our bodies in response to exercise and how those changes relate to human health.
In FY 2019, NIAMS plans to continue support for its Research Innovations for Scientific Knowledge (RISK) funding opportunities, which allow investigators from around the country to submit cutting edge, unconventional, innovative research proposals for up to three years of funding. To help bolster the next generation of researchers, the Institute also continues to encourage early established investigators who have successfully renewed their first NIAMS research project grant to apply for a supplemental funding program to aid the transition of their individual research project into a broader, more robust and resilient research program.