The Lupus Research Institute (LRI) today announced the first $1 million research grants given to lupus investigators by a private research organization. The LRI Distinguished Innovator Initiative was created to address the current lack of treatments in development that could arrest or reverse the disease. The first privately funded awards of this scale in lupus, it challenges the international scientific community to pursue highly promising new ideas on the fundamental causes of lupus that can lead to a cure.
The two Distinguished Innovator recipients, Drs. Ann Marshak-Rothstein at University of Massachusetts Medical School and Greg Barton at University of California, Berkeley, independently zeroed in on one family of proteins called Toll-like receptors as key triggers of the body's devastating autoimmune attack on itself that characterizes lupus. Because TLR proteins are essential in fighting any infection, how the body loses control over their activity is a fundamental question in immunology. Finding the causes of lupus, the prototype for autoimmune disease research, could have broad implications across a wide range of illnesses affecting millions.
Which Toll-like receptor is responsible?
Dr. Marshak-Rothstein's research group was the first to propose that the TLRs could have a primary role in lupus by turning on the immune system to attack the body. Recent animal studies found that one TLR, TLR7, has a harmful role, while another, TLR9, has the opposite effect helping to protect against lupus.
Building on that work, Dr. Marshak-Rothstein is developing a highly innovative experimental approach to pinpoint which specific TLR is mainly to blame for causing lupus in humans. This experimental approach also promises to reveal new targets for therapies that could prevent or arrest lupus.
Dr. Marshak-Rothstein noted, "Support from the LRI will enable us to extend our analysis of the cell components recognized by TLRs in mice to TLR activation in human cell populations, and allow us to identify those patients most likely to respond to therapies directed at blocking specific TLRs."
Why Don't TLR's Harm Healthy People?
Also focusing on TLRs as prime suspects, Dr. Barton seeks to solve why TLRs cause a problem in people with lupus but not in healthy people. His work will determine if the reason the lupus immune system begins to attack its own DNA might lie with proteins inside immune cells whose job is to control TLR activity. Dr. Barton anticipates proving that lupus patients have defects in these control proteins that allow TLRs to mistakenly switch into action.
Dr. Barton's study seeks to pinpoint the earliest errors made by the lupus immune system and suggest new treatments to correct them. His investigations also have broad implications for autoimmune disease, infectious disease and beyond. The new knowledge generated by his work could even inform vaccine design against infectious diseases or cancer.
"In the last few years, we have started to learn how the immune system regulates TLRs," said Dr. Barton. "The next challenge, and the focus of our work, is to determine whether differences in these processes can explain why certain people develop lupus while others do not."
Stellar First Year for New Distinguished Innovator Award Initiative
The LRI received applications for the first privately funded $1 million grants from many of the world's most renowned scientists as well as rising young investigators with great promise for contributing their talent to uncovering the causes of lupus. Rigorous peer-review was conducted by a team of LRI's scientific advisors and 12 of the world's leading lupus experts.
"We were enormously impressed by the quality of the submissions and the two from Drs. Barton and Marshak-Rothstein stood out as offering the best possibilities for key insights," noted world-leading immunologist Dr. William Paul, LRI Scientific Advisory Board Chairman and National Academy of Sciences member. "With these Distinguished Innovator awards and existing annual Novel Research Grants, the LRI continues to pursue a strategy of funding the most innovative and novel research that has had unprecedented success in driving new answers in a complex disease state. Their work over the past decade has provided the basis for this transformative research initiative to look for the fundamental causes of lupus that can drive to a cure and the means to prevent lupus."
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