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. These trials have encompassed a variety of approaches to immunosuppression. The most recent trial - a pilot trial of the anti-thyroid drug methimazole 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. This trial was completed in the past year. Patients with active myositis received a 6-month trial, with muscle biopsies being performed for research purposes at the beginning and three months into therapy. The level of mRNA of MHC Class I & II in muscle tissue and simultaneously-obtained peripheral blood monocytes was measured by Northern analysis. Patients were assessed carefully clinically, and the presence of inflammation in the quadriceps was measured by MRI. The MRI analysis employed 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. An attempt is being made, in collaboration with the laboratory of Eric Hoffman at Children's National Medical Center, to determine the effect of the drug on gene expression in affected muscle tissue.In collaboration with the Alexion Corporation, we have begun a trial of a recombinant humanized antibody (H5g) directed at the late part of the pro-inflammatory complement pathway, anti-C5, in dermatomyositis. In that illness, activation of the late components of complement has been shown. The trial is double-blind, with a weekly infusion for two months. 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 member of ARB who now works at CBER, FDA and volunteers in the ARB clinic.
