Mystery solved: Gold's power against autoimmune diseases defined

[Guest guest]

Public release date: 26-Feb-2006

[ Print Article | E-mail Article | Close Window ]

Contact: Lacey

public_affairs@...

617-432-0442

Harvard Medical School

Mystery solved: Gold's power against autoimmune diseases defined

BOSTON, MA– 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 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

DeDecker, PhD, HMS post-doctoral student in the Department of

Cell Biology and a study co-author. At the time of this work,

DeDecker was in the Harvard Medical School 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 De Wall, PhD, 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 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 their search through thousands of compounds they found that

the known cancer drug, Cisplatin, a drug containing the metal

platinum, directly stripped foreign molecules from the MHC class II

protein. From there, they found that platinum was 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

researches a mechanism of gold drug action that can be tested and

explored directly in diseased tissues.

In 1890, a German doctor named 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 use in

recent years.

With this new understanding of how these metals function, it may now

be possible to develop a new generation of gold-based drugs for

treating rheumatoid arthritis and other autoimmune diseases that are

more effective with fewer side effects.