The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) conducts and supports basic, translational, and clinical research on some of the most debilitating diseases affecting the Nation’s health. Although a number of these diseases are very common, many of them are rare, affecting only a few thousand people world-wide. In this month’s letter, I will highlight several examples of NIAMS-funded research on rare diseases. The importance of studying these conditions cannot be overstated. Research on rare diseases has tremendous potential to improve the lives of affected individuals. It also substantially advances our understanding of fundamental biology, and therefore often provides insights that can be applied to other diseases that affect larger numbers of people.
In July, I had the opportunity to highlight NIAMS support for research on rare heritable connective tissue disorders at a Capitol Hill briefing sponsored by the Marfan Foundation. I discussed NIAMS-funded research on two disorders, Marfan syndrome and epidermolysis bullosa (EB). In Marfan syndrome, the connective tissue found throughout the body is abnormal, affecting many systems adversely, including the skeleton, eyes, heart and blood vessels, nervous system, skin, and lungs, and in some cases, leading to cardiovascular complications that are life threatening. NIAMS supports basic research to improve understanding of the genetic mutations and molecular mechanisms that cause Marfan syndrome. These investigations formed the basis for clinical trials of a new therapy for Marfan syndrome.
In EB, individuals lack proper collagen VII fibers, which are key structural proteins in the skin. The condition results in extremely fragile skin and mucous membranes that break and blister easily. The wounds are difficult to heal, and when they do, extensive scarring can occur that, at times, lead to devastating squamous cell carcinomas. The Institute supports basic research on potential therapies that replace collagen, either through topical or intravenous administration, and funds clinical research to determine whether genetically modified skin grafts can be used to treat patients with EB. Results of the research could have broad implications for treating traumatic wounds in the general population.
Also last month, a team of NIAMS researchers led by Dr. Raphaela Goldbach-Mansky, Acting Chief of the Translational Autoinflammatory Disease Section, reported the identification of the gene responsible for STING-associated vasculopathy with onset in infancy (SAVI), a rare autoinflammatory disease. SAVI symptoms, which manifest in early infancy, include systemic inflammation, vascular lesions affecting the fingers, toes, nose, and ears, and inflammation and scarring in the lungs. By analyzing the DNA of affected children and their parents, the researchers were able to identify the genetic mutation that causes the disease, and show that it leads to overproduction of interferon, a major driver of inflammation. The research team has now begun testing whether drugs that block interferon signaling can be used to treat patients with SAVI. This research provides important insights about the molecular mechanisms of the immune response that can be applied to other diseases. More information about the study can be found on the NIAMS website.
Finally, in my February letter, I wrote about neonatal-onset multisystem inflammatory disease (NOMID). Like SAVI, NOMID is a rare autoinflammatory disease that also was characterized by Dr. Goldbach-Mansky and her colleagues. Now, a short video developed by the Institute provides a more personal view of how rare diseases affect the lives of patients and families. The video tells the story of Kayla, a young NOMID patient who is treated at the NIH Clinical Center. It also features Kayla’s mother and Dr. Goldbach-Mansky. I appreciate their willingness to share their experiences and to convey, in a very powerful way, why we do this work.
Thus, research on rare diseases not only brings new knowledge and potentially new treatments to affected patients, but also provides us with a greater understanding of the biological systems that affect human health.