Leading the way to a cure

Lupus Research Update: 2010 Volume 3

Volume 3, 2010 - Online Edition | In This Issue

A Major Advance in Use of Steroids >
Faces of Lupus: CELEBRATING 10 YEARS >
The Role of Vitamin D in Lupus >
Registries Help Guide Lupus Research and Treatment >
Milestones in an Illustrious 10-Year History >
Lupus News Corner >

A Major Advance in Use of Steroids

Steroids are widely used for a diverse array of medical purposes... including autoimmune diseases. Yet for all of its benefits, this therapy is no cure-all. In fact, it can cause serious internal damage — especially for people with lupus.

Today, new findings from an ALR-funded investigation are changing our concept of steroids. The collaborative effort is led by Dr. Virginia Pascual, principal investigator at Baylor Research Institute (BRI) in Dallas, and Dr. Franck Barratt, director of drug discovery at Dynavax in Berkeley.

These scientists have discovered that two immune system proteins undo much of the therapeutic action of steroids, thereby requiring larger doses of steroids and increasing the risk of further side effects.

Steroids essentially kill certain malfunctioning immune system cells, including plasmacytoid dendritic cells (PDCs), which generate too much type 1 interferons — a contributing cause of lupus and other autoimmune diseases.

But two immune system proteins toll-receptors named TLR7 and TLR9 make conditions worse by activating additional PDCs. They increase the supply of the very cells that steroids are killing. So more and more steroids have to be used to keep down the PDCs.

Steroids work by stopping a hyperactive immune system from attacking healthy tissues. But for some reason, steroids have been less effective in people with lupus — and an investigation funded by ALR has discovered the cause.

“We have long known that these receptors play a critical role in lupus, but until now, we didn’t know that they were directly interfering with the effects of steroid treatments,” said Virginia Pascual, M.D. “By blocking TLR7 and TLR9 function, we may have found a safer way to treat this debilitating disease.”

Dr. Pascual’s work is welcome news to lupus sufferers because the large dosage of steroids now required for treatment can cause serious damage to the organs as well as weight gain, cataracts, hypertension, and brittle bones. And in children steroids can also stunt growth.

“Lupus is definitely a very challenging and serious disease in children,” said Dr. Pascual. “The treatments used to quell flares and maintain remission have many physical and emotional effects that can lead to negative self-esteem issues.”

Much of Dr. Pascual’s investigation is focused on children, which is a departure from most research in lupus. The findings are expected to apply equally well to adults with the disease.

Both ALR grantees, Dr. Pascal received two grants totaling $1.5 million in 2003 and 2005, and Dr. Barratt received one grant for $483,000 in 2004. In total, the ALR has granted $8 million to TLR research.

Progress is moving fast. Blocking agents for TLR7 and TLR9 are already in development and are expected to be ready for clinical trials soon. The ALR is proud to have been part of this pioneering and hopefilled study.

1.5 million

people in the U.S. have Lupus.

172 million

dollars committed to lupus research by the Lupus Research Alliance.

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