LRI: A Champion of Brilliant Ideas and Promising New Investigators

A key Lupus Research Institute (LRI) tenet is "to go where the science leads," allowing investigators to pursue bold yet sound scientific hypotheses unimpeded by conventional thinking. Formulated by senior scientists and lupus community leaders, this strategy recognizes that most major breakthroughs in medicine emerge from unexpected directions.

And lupus needs a breakthrough. There hasn't been a major new treatment approved for this devastating autoimmune disease in more than 40 years. No targeted anti-inflammatory drugs. No refined treatments for lupus rash, kidney disease (lupus nephritis), extreme fatigue, swollen joints, or tools for better assessing the signs and symptoms of lupus. No simplified diagnostic measure to promote prevention.

"The current treatments we have for lupus are the same that I had when I started my practice in 1979, with a very few minor exceptions," notes Daniel J. Wallace, MD, clinical professor of medicine at the Cedars-Sinai Medical Center/David Geffen School of Medicine at UCLA and an LRI board member.

Keen Minds + High Caliber Science

The accomplishments of LRI-funded researchers have raised hope that progress toward prevention, better treatment, and a cure for lupus are finally within sight.

Researchers have achieved major scientific breakthroughs in uncovering mechanisms and potential treatments for numerous complications of lupus (systemic lupus erythematosus, S.L.E.) and discoid (skin) lupus. They have shed light on genetic links to lupus, pinpointed the role of B-cells and certain types of white blood cells in the disease process, and provided a better understanding of how lupus attacks the brain, kidney, and skin.

Examples include Victoria Werth, MD, and her team at the University of Pennsylvania, which identified a variant of the human gene for tumor necrosis factor-alpha as a cause of photosensitivity in lupus. Betty Diamond, MD, and her research team identified anti-DNA antibodies that bind to nerve-cell receptors in the cerebral cortex of the brain, causing the cells to die. This represents the first real clue to mental impairment in people with lupus.

And in a major breakthrough on heart disease in lupus, Bevra H. Hahn, MD, and Maureen McMahon, MD, have described a subtype of the normally "good" high density lipoprotein (HDL) cholesterol that appears to play a destructive role in people with lupus and rheumatoid arthritis, promoting atherosclerosis (hardening of the arteries) and heart disease in many of these individuals. One day soon doctors may be able to test people with lupus for this menacing HDL form—pro-inflammatory HDL (piHDL)—and be able to take measures to aggressively treat (prevent or reverse) the damage it can do.

Findings are widely published in the best journals, including Arthritis & Rheumatism, The Journal of Rheumatology, and Science. For a sampling of LRI-funded research findings published so far, see News.

To expedite lupus drug development, better assess lupus disease activity, and measure organ damage and response to therapies, LRI scientists consider it crucial to identify and validate "early predictors" called biomarkers.

"The LRI is a catalyst," explains LRI Scientific Board Chairman William Paul, MD, chief of the laboratory of Immunology at the NIH National Institute of Allergies and Infectious Diseases. "It brings innovative work to the fore and allows investigators to get the information they need to then command the much larger sums of money that the NIH and the pharmaceutical industry can bring to bear."