Dear Supporters, Friends, and Colleagues,
As many of you know, the American College of Rheumatology Annual Scientific Meeting is an important medical meeting for those who perform lupus research. More than 8,000 physicians, physician-scientists, scientists and other health professionals from around the world attend. Some 2,000 research studies on the latest advances in rheumatic disease are discussed. We are proud that at the last meeting in November 2005, about two-thirds of our ALR grantees presented papers—some several—and a significant number were related to work supported by our grants. Here are six of particular interest.
One paper from Robert Eisenberg, MD, University of Pennsylvania, an investigator supported by the ALR for several years, focused on rituximab. This promising drug induces remission in some people with lupus, apparently by depleting B cells and “resetting” their immune systems. Dr. Eisenberg and his colleagues analyzed patients they have treated with rituximab, comparing those whose B cells were fully versus partially depleted and beginning to define those clinical features associated with either outcome. These and ongoing studies will better define the relationship between the B cell count, other parameters, and efficacy of the drug.
Another important paper focused on pregnancy loss in women who have antiphospholipid antibodies, a problem frequently encountered by women with lupus. The senior author, Jane E Salmon, MD, Hospital for Special Surgery, New York, reported that the research grew out of work supported by her 2003 ALR grant. She and her colleagues found that a substance called tissue factor, which initiates the coagulation cascade, is the link between inflammation and thrombosis (blood clots) in miscarriages induced by antiphospholipid antibodies, potentially defining a new target to prevent pregnancy complications in lupus.
One session with several papers focused on bringing research from the lab bench to the bedside. Nilamadhab Mishra, MD, Wake Forest University School of Medicine discussed his currently-funded ALR work in this session. His group has shown that lupus may be associated with changes in gene activity resulting in part from abnormalities in the actions of HDAC (histone deacetylase) enzymes, molecules in the nucleus of cells that can alter activity, or expression, of genes and thereby contribute to inflammation in lupus. They have now demonstrated that HDAC inhibitors may not only treat lupus but simultaneously prevent or decrease premature atherosclerosis. (More on Mishra’s work on page 3.) In this session Timothy Behrens, MD, University of Minnesota, a long-term ALR grantee, presented two papers directly related to work we funded. His group used genomic technology to identify proteins regulated by interferon—and elevated in people with lupus—that may be convenient biomarkers for predicting disease activity. Michelle Petri, MD, Johns Hopkins University School of Medicine, also an ALR grantee, was another investigator participating in this project. (See page 2 for more on this work.)
Another paper found that a particular gene may influence the expression of specific SLE manifestations and that these associations may vary according to ethnic background. Such work may eventually help improve diagnosis and enable the targeting of various treatments to those individuals most likely to benefit. This study was supported by an ALR grant to Marta E. Alarcon-Riquelme, MD, University of Uppsala, Sweden, whose work we have been funding since 2004.
These are just a few of the research papers that demonstrate the success of the ALR research program. We are proud of this fine body of work and the role the ALR has played in bringing it to fruition.
Joseph Craft, MD
Chair, Scientific Advisory Board
Through the long-term advocacy efforts of the ALR to generate lupus research dollars from the Department of Defense (DoD), lupus was added to its Peer Reviewed Medical Research Program (PRMR) in 2005. The ALR encouraged lupus investigators across the country to pursue these grants and provided guidance for the application process, yielding about 30 applications. We are delighted that the DOD has awarded two grants to lupus investigators. Their research will benefit all people with lupus.
Potential grantees were required to show relevance of the grants to the mission of the DoD, and George C. Tsokos, MD, principal investigator of one of the grants, made the point well. “The Armed Services have a high ratio of African Americans, Hispanics, and Asians, who have a higher prevalence of lupus than the Caucasian population, making it particularly important for the Department of Defense to have tools for more accurately diagnosing and monitoring lupus activity—which is the focus of both these grants,” said Dr. Tsokos. “It is critically important for commanders to be able to determine when personnel will be expected to flare and when they will respond to treatment.”
Dr. Tsokos, Professor of Medicine and Molecular Biology at the Uniformed Services University in Bethesda, MD, will work with co-investigators Joseph M. Ahearn, M.D. and Susan Manzi, MD, MPH, Co-Directors of the Lupus Center of Excellence at the University of Pittsburgh Schools of Health Science. This four-year $1.5 million collaborative project is focused on T cell biomarkers. The study will capitalize on the Pittsburgh Lupus registry which totals more than 1,000 people with lupus who have been recruited by Dr. Manzi. Recent studies of this cohort have led to development of a panel of promising complement-based biomarkers through funding by the ALR. Support from the DOD will now facilitate investigation of distinct but related biomarkers developed in the Tsokos laboratory. The expectation is that this work will ultimately lead to both an arsenal of lupus biomarkers and to additional clues regarding pathogenesis.
Timothy W. Behrens, MD, Professor of Medicine at the University of Minnesota, will work on a four-year, $1 million research project validating another approach to biomarkers. He will use a biorepository of over 2,000 blood samples from people with lupus to validate gene expression signatures as biomarkers for disease activity and severity in SLE. Dr. Behrens’ study is directly related to work funded under his earlier ALR grant on identifying an interferon gene expression signature in SLE.
This year, the ALR’s advocacy efforts have continued to press for inclusion of lupus in the PRMR of the DoD, and Congress recently signed a bill guaranteeing it. Since the PRMR is a $50 million research program, we look forward to further support for lupus in next year’s round of submissions.
To read more on the latest in lupus research, click here to download the most recent Lupus Research Update.
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