Gold compounds have been used for the treatment of rheumatoid arthritis and other autoimmune diseases for more than 75 years, but, until now, how the metals work has been a mystery. Harvard Medical School (HMS) researchers report in the Feb. 27 issue of Nature Chemical Biology that special forms of gold, platinum, and other classes of medicinal metals work by stripping bacteria and virus particles from the grasp of a key immune system protein.
“We were searching for a new drug to treat autoimmune diseases,” says Brian DeDecker, HMS postdoctoral student in the Department of Cell Biology and a study co-author. At the time of this work, DeDecker was in the HMS Institute of Chemistry and Cell Biology, which uses powerful chemical tools to illuminate complex biological processes and provide new leads for drug development. “But instead we discovered a biochemical mechanism that may help explain how an old drug works.”
DeDecker and co-author Stephen De Wall undertook a large-scale search for new drugs that would suppress the function of an important component of the immune system, MHC class II proteins, which are associated with autoimmune diseases. MHC class II proteins normally hold pieces of invading bacteria and viruses on the surface of specialized antigen presentation cells. Presentation of these pieces alerts other specialized recognition cells of the immune system, called lymphocytes, which starts the normal immune response. Usually this response is limited to harmful bacteria and viruses, but sometimes this process goes awry and the immune system turns toward the body itself, causing autoimmune diseases such as juvenile diabetes, lupus, and rheumatoid arthritis.