The Connective Tissue and Diseases Section began studying inflammatory myopathies (polymyositis, dermatomyositis, and related diseases) some years ago in an attempt to understand the relationship of autoantibodies to autoimmune disease. These diseases seemed to offer the best example of autoimmune diseases associated with highly specific disease-related autoantibodies and evidence of a viral etiology. They are very uncommon and hence relatively less studied than other autoimmune diseases, and they are very debilitating and hence in need of improved therapy. In order to attract patients here to allow more detailed clinical, immunological, genetic, and viral studies, we began doing trials of therapy and have completed a number of such studies. They are among the very few published controlled trials in this difficult to treat family of illnesses. A trial of the purine analog, flurodeoxyadenosine, has been analyzed, and the results have been published in the past year. A pilot trial of the anti-thyroid drug methimazole has been continued and the treatment regimen intensified and prolonged. This trial was undertaken to make use of an unexpected property of the drug which was discovered by Dr. Leonard Kohn of NIDDK and Dr. Dinah Singer of NCI: that it can down-regulate MHC. Patients with active myositis are receiving a 6-month trial, with muscle biopsies being performed for research purposes at the beginning and 3 months into therapy. The level of mRNA of MHC I & II in muscle tissue and simultaneously-obtained peripheral blood monocytes is measured by Northern analysis. Patients are assessed carefully clinically, and the presence of inflammation in the quadriceps is measured by MRI. The MRI analysis will employ a computer-based measure of tissue edema on the STIR image which was recently published by our group along with the Department of Radiology in the Journal of Magnetic Resonance Imaging. It is expected that this trial will be concluded and analyzed within the coming year.New myositis trials being considered are likely to involve new agents developed for the treatment of rheumatoid arthritis, such as anti-TNF agents (Embrel) and leflunomide (Arava) and at least one novel biologic agent. It is likely that these will be short-term trials in which surrogate markers, including MRI, are used to assess outcome.Dr. Lisa Rider has continued to examine patients with juvenile myositis at the Clinical Center and to lead a collaborative group of pediatric rheumatologists throughout the country and in Canada in a thorough clinical and laboratory description of the disease. Dr. Rider is a former members of ARB who now works at CBER, FDA and volunteers in the ARB clinic. - myositis, polymyositis, dermatomyositis, immunosuppression, MHC, methimazole, clinical trial - Human Subjects
