David S. Pisetsky, MD, PhD

Duke University Medical Center, Durham, NC

2003/2004 Biomarkers

With LRI funding, Dr. Pisetsky and his colleagues set out to determine if a newly discovered mediator of inflammation known as high mobility group 1 protein (HMGB1) might be effective in treating lupus.

“What one would like to do is to develop new, more specific, and less toxic approaches to suppressing the abnormal immune reaction in lupus. Anti-HMGB1 treatment may represent such an approach,” said Dr. Pisetsky.

Discovery: Old Arthritis Drug—Gold Salts—Blocks a Cause of Inflammation in Autoimmune Disease

The inflammation-causing molecule, HMGB1, has been implicated in a broad range of immune-mediated diseases. When the immune system is fighting disease, HMGB1 signals immune cells such as T-cells to travel to the infection site and produce antibodies and kill infected cells directly.

“There’s a lot of interest in the role of HMGB1 in lupus,” Dr. Pisetsky said.

In 2007, Dr. Pisetsky and colleagues reported that gold salts, which are a well-established arthritis treatment, interfere with white blood cells and prevent them from releasing HMGB1. His findings provide are the first to demonstrate that a disease-modifying anti-rheumatic drug can actually decrease the release of this inflammatory mediator.

Might HMGB1 reduce the inflammatory symptoms of lupus?

Dr. Pisetsky doubts that existing gold-based drugs, which have fallen from favor because of their side effects, will be reintroduced as lupus treatments.

But if his team can identify the molecular pathway that gold salts act on, they might be able to screen for other, less toxic, drugs that similarly block HMGB1.

Dr. Pisetsky is also investigating the potential of HMGB1 as a biomarker (early marker) of lupus disease activity.

Select publications:

Pivotal advance: inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate. Zetterström CK, Jiang W, Wähämaa H, Ostberg T, Aveberger AC, Schierbeck H, Lotze MT, Andersson U, Pisetsky DS, Erlandsson Harris H. J Leukoc Biol. 2008 Jan;83(1):31-8. Epub 2007 Oct 3.

Ongoing funding:

Dr. Pisetsky won a 5-year, $1.8 million grant from the NIH, as well as a $300,000 Veteran’s Association award to continue the work that he initiated with LRI funding.

Back