These drugs are as good as gold

Gold components 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. Researchers from Harvard Medical School, Boston, report 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, but instead we discovered a biochemical mechanism that may help explain how an old drug works," admits Brian DeDecker, a post-doctoral student in the Department of Cell Biology.

DeDecker 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. These proteins normally hold pieces of invading bacteria and virus 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 towards the body itself, causing autoimmune diseases such as juvenile diabetes, Lupus, and rheumatoid arthritis.

During the search through thousands of compounds, DeDecker found that the known cancer drug Cisplatin, which contains the metal platinum, directly strips foreign molecules from the MHC class II protein. From there, he discovered that platinum is just one member of a class of metals, including a special form of gold, that all render MHC class II proteins inactive.

In subsequent experiments in cell culture, gold compounds were shown to render the immune system antigen presenting cells inactive, further strengthening this connection. These findings now give scientists a mechanism of gold drug action that can be tested and explored directly in diseased tissues. In 1890, a German physician named Robert Koch found that gold effectively killed the bacteria that caused tuberculosis. In the 1930s, based on a widely held--but probably erroneous--connection at the time between tuberculosis and rheumatoid arthritis, a French doctor, Jacques Forestier, developed the use of gold drugs for the treatment of rheumatoid arthritis.

Gold drugs have been used since then as an effective treatment for this and other autoimmune diseases such as Lupus, but treatment can take months for action and sometimes presents severe side effects, which have diminished their utilization in recent years.

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