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MUSC poised for scleroderma research success by Cindy Abole Public Relations Imagine a patient receiving news that he or she has been diagnosed with a disease that they or others know very little about. That's the reaction of many newly-diagnosed scleroderma patients as they begin to live and cope with this little-known, chronic autoimmune disease that affects the skin and internal organs in more than 300,000 Americans. For the first time, MUSC is playing a dynamic role in scleroderma research by participating in  two NIH-funded research studies that will not only contribute new knowledge to this systemic disease but will ultimately lead to improved treatments that will improve the quality of life for scleroderma patients everywhere. “We're at the threshold of seeing how today's biotechnology is being applied to more common diseases like rheumatoid arthritis (RA), where certain therapies have made a dramatic difference in the lives of many RA sufferers,” said Richard Silver, M.D., professor of medicine and pediatrics and director, Division of Rheumatology and Immunology. “We're hoping to see the same type of success for  scleroderma patients.” Scleroderma  is defined as a chronic and degenerative disorder that causes a thickening and tightening of the skin that can lead to vascular deterioration, tissue loss, and an  overproduction of collagen in the body's connective tissue. It is most serious when it affects internal organs, causing severe damage and serious complications to the body's digestive, respiratory, circulatory and immune systems. Silver heads MUSC's involvement in the $8 million-funded Scleroderma Lung Study, a national collaboration involving rheumatologists and pulmon-ologists to study the effects of a medication for the treatment of lung disease in scleroderma patients. The study, funded by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH), focuses on the effectiveness of the drug cyclophosphamide or Cytoxan, an immunosuppressant drug that has shown promise for its effectiveness in scleroderma. “It's exciting to be a part of a multi-center trial that allows us to work with other scleroderma experts who are involved in other related studies,” said Marcy Bolster, M.D., associate professor of medicine, Division of Rheumatology and Immunology and a co-investigator of the study. Bolster works with Charlie Strange, M.D., associate professor of Pulmonary and Critical Care Medicine on this study. The multi-center, placebo-controlled trial is the first of its kind and is open to patients with active lung disease, possibly the biggest cause for scleroderma morbidity and mortality. Participants receive a  50/50 chance of receiving the drug or placebo as part of the year-long study to prove its efficacy. According to Bolster, its effect will be an important step in altering lifestyle and mortality. MUSC will also share an important role as the study's bronchoalveolar lavage (BAL) core facility. Lung inflammation and fibrosis or scarring are common conditions in scleroderma patients. The amount of inflammation can be measured through BAL, a procedure that uses a flexible bronchoscope, which examines cells specifically in a section of the lung. MUSC will be involved in selecting and monitoring patients, plus processing and storing of study samples. “Certainly, a lot of patients with scleroderma are affected by lung involvement, but not all of them have active inflammatory disease,” Bolster said.  As with diseases of this nature, the study incorporates the multidisciplinary expertise of MUSC specialists throughout campus including rheumatology, pulmonary, radiology, pharmacy, the General Clinical Research Center (GCRC) and other departments. Silver and his colleagues and MUSC scleroderma patients have enjoyed a long-standing relationship with the GCRC for continued care and treatment.  “The relationship between clinician and basic scientist in this study is also important,” Bolster said, referring to the different roles each participant undertakes. Silver, Strange and  Bolster will review, study and interpret BAL slides, while scientists process BAL fluid samples sent by other centers and prepare them for storage. “Certainly, there are other chronic diseases that are more common than scleroderma such as cardiovascular disease and diabetes, which have always received more funding,” Bolster said. “Scleroderma research has always been limited. That's another reason why this study is exciting for us. It has given us significant NIH recognition with grant support.” Beyond MUSC, the study incorporates active participation from rheumatology and pulmonary staffs at Boston University, Georgetown University, Johns Hopkins University, the University of Colorado, University of Alabama-Birmingham, UCLA, University of Illinois, University of Medicine and Dentistry of New Jersey, University of Pittsburgh, Virginia Mason Research Center-Seattle and Wayne State University.  New Collagen Tolerance Study Another NIH-funded study involves the study of scleroderma and skin. The Oral Bovine Collagen Tolerance Study is a three-year trial involving eight national test sites devoted to study skin fibrosis. The study focuses on confirming and modulating an immune response that can reduce fibrosis and scarring. “Scleroderma patients usually suffer from scarring or hardening of skin caused by fibrosis,” said Clarence Legerton, III, M.D., a rheumatologist and associate professor working in the Division of Rheumatology and Immunology. “What we're hoping to determine is if collagen can induce an abnormal immune response or help regress or stop skin involvement in the disease.” Collagen is an insoluble, fibrous natural protein produced in the body and usually found in the white fibers of connective tissue, cartilage and bone. Legerton, with co-principal investigator Edwin A. Smith, M.D., professor, Division of Rheumatology and Immunology, are seeking and enrolling 10 qualified patients. Study patients must be at least 18 years of age and diagnosed with diffuse scleroderma. “The study will help us answer two important questions: the effectiveness of collagen in a pathogenetic role and its helpfulness among patients,” Legerton said. “The therapeutic use of ace inhibitors and other drugs, plus other good advances have been helpful in managing problems with visceral organs and other complications related to this disease.” Since 1992, Legerton has been involved in other related research including osteoarthritis, rheumatoid arthritis, as well as scleroderma. “Until we are able to find one medication that will cure all features of this disease, we're left with finding treatments for each organ system individually,” Silver said.  Scleroderma database is key Since arriving in 1991 as a Rheumatology fellow at MUSC, Marcy Bolster, M.D., has held a keen interest in studying scleroderma.  In fall 1997, she helped develop MUSC's computerized database for scleroderma patients. Patterned after a successful 20-year database of scleroderma patients at the University of Pittsburgh, Bolster hopes to record patient information that will be helpful in a group analysis of the disease. “There's a lot of basic science research that occurs in our division and to be able to coordinate that with clinical information is a real asset,” said Bolster, referring to the ability to look at sub-groupings of patients based on specifics such as lab, clinical and medication features.” Members of the Division of Rheumatology and Immunology treat scleroderma patients from a wide geographic area, as far west as Kentucky. According to Bolster,  researchers can use the database to analyze the blood work of scleroderma patients, while extracting other valuable information from demographic data to disease characteristics within individuals. Bolster, who also conducts clinical trials in the areas of rheumatoid arthritis and gout, devotes much of her work on the clinical investigation and treatment of scleroderma. “So far, it has been a very rewarding learning experience,” Bolster said, of her research and clinical work while at MUSC. “The collaboration between rheumatology and pulmonary is tight and interactive. That's what makes it great.”