Neuropsychiatric Lupus Research Receives a Boost

Five new research grants on the neuropsychiatric aspects of lupus have been funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health (NIH), a part of the Department of Health and Human Services (DHHS). The grants, totaling more than $1.2 million for FY 2002, include both basic and clinical research studies. Co-funding was provided by the Office of Research on Women's Health (ORWH).

"These research grants will increase our understanding of the disease's nervous system complications. Neuropsychiatric symptoms can be particularly distressing for people with lupus and their families," said Stephen I. Katz, M.D., Ph.D., director of the NIAMS.

Systemic lupus erythematosus (SLE) is an autoimmune disease that mainly affects women of childbearing age. Common symptoms of SLE may include painful or swollen joints, unexplained fever, skin rashes, kidney problems, and extreme fatigue. In addition, there are a wide variety of associated neurological and psychiatric syndromes, which have been placed under the heading of Neuropsychiatric-SLE (NP-SLE). Examples include stroke, depression, inflamed cerebral blood vessels, seizures, headaches, and cognitive dysfunction (disordered thinking). NP-SLE affects more than 20 percent of lupus patients and is one of the major causes of death among people with lupus. The following projects will apply new tools and approaches to the discovery of the underlying causes of NP-SLE. Ultimately, this may lead to improved diagnosis and treatment for patients with NP-SLE.

The new studies include:

Brain Connections, Michelle Petri, M.D., Johns Hopkins University, Baltimore, Md. Investigators in this multicenter study will measure cognitive dysfunction and biological changes and will perform brain imaging in newly diagnosed neuropsychiatric lupus patients. This work could lead to the discovery of early disease mechanisms that may be responsive to treatment. Brain Cell Death in MRL Mice: Targets and Mechanisms, Boris Sakic, Ph.D., McMaster University, Hamilton, Ontario, Canada. The mechanisms responsible for cell death in the brains of autoimmune mice with lupus-like neuropsychiatric symptoms will be investigated. Central nervous system malfunctioning and its effects on behavior will be assessed. New research approaches to understanding the progression of central nervous system damage are likely to be uncovered.

Cognitive Dysfunction in Neuropsychiatric SLE, Michael Lockshin, M.D., Hospital for Special Surgery, New York, N.Y. This research will combine clinical, biological and imaging approaches to identify subgroups of SLE patients. SLE patients will be followed to determine the relationship between imaging abnormalities, a specific receptor antibody, lupus symptoms and heart disease. By studying the biological mechanisms underlying lupus brain injury, this research will assist in redefining the progression of cognitive dysfunction in SLE patients and will suggest new targets for treatment.

Antibodies to NR2 in SLE, Betty Diamond, M.D., Albert Einstein College of Medicine, Bronx, N.Y. In this project, the mechanism of brain dysfunction in SLE will be examined. Antibodies that bind to the DNA of people with lupus can also bind to the NR2 receptor on neurons and cause cell death. Mouse models of SLE will be studied using brain imaging and other measurements to test antibody binding to the NR2 receptor as a possible pathway to the neurological symptoms some people with lupus experience. This project will help to build a scientific foundation for the development of therapies to prevent central nervous system damage in lupus.

Identifying Genes for Neuropsychiatric Lupus, Mishra Nilamadhab, M.D., Wake Forest University School of Medicine, Winston-Salem, N.C. This study seeks to discover the genes responsible for the neurological symptoms of lupus by examining mouse models. Uncovering the genetic basis for neuropsychiatric lupus is a necessary precursor to the development of targeted therapies.

The award of these grants is the result of a special solicitation for research applications, AR-01-007, entitled "Neuropsychiatric Systemic Lupus Erythematosus" (http://grants1.nih.gov/grants/guide/rfa-files/RFA-AR-01-007.html). This RFA was based in part on the scientific opportunities identified in the workshop "Neuropsychiatric Manifestations of Systemic Lupus Erythematosus" held at NIH in May 1999. A summary of the workshop can be found at http://www.niams.nih.gov/ne/reports/sci_wrk/1999/reportnmsle.htm.

For more information on lupus, contact:

American College of Rheumatology 1800 Century Place, Suite 250 Atlanta, GA 30345 Phone: 404-633-3777 Fax: 404-633-1870 www.rheumatology.org

Arthritis Foundation 1330 West Peachtree Street Atlanta, GA 30309 Phone: 404-872-7100 or 800-283-7800 (free of charge) or your local chapter listed in the telephone book www.arthritis.org

Lupus Foundation of America 1300 Piccard Drive, Suite 200 Rockville, MD 20850 Phone: 301-670-9292 or 800-558-0121 (free of charge) or your local chapter listed in the telephone book www.lupus.org

SLE Foundation 149 Madison Avenue, Suite 205 New York, NY 10016 Phone: 212-685-4118 or 800-74-LUPUS (745-8787) (free of charge) www.lupusny.org

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

The Office of Research on Women's Health (ORWH) was established in September 1990 within the Office of the Director, NIH. ORWH works in partnership with the NIH institutes and centers to ensure that women's health research is part of the scientific framework at NIH and throughout the scientific community. For more information about ORWH, call (301) 402-1770 or visit the ORWH Web site at http://www4.od.nih.gov/orwh/.