2001-2002 Arthritis National Research Foundation Grants:
Studying Causes, New Treatments for Arthritis

LONG BEACH, CA -- The Arthritis National Research Foundation (ANRF) has funded eight scientific studies investigating how arthritis occurs in the body. As the mechanisms of these diseases are more fully understood, new and better therapies may be developed. One in six Americans -- over 43 million -- suffers with arthritis.

Much of the new research and therapies involving the interruption of the inflammatory disease process, call anti-Tumor Necrosis Factor (TNF) treatments, are the direct result of discoveries funded by ANRF in the 1980's.

The Arthritis National Research Foundation is committed to funding the work of researchers developing new therapies intended to improve the quality of life for arthritis sufferers. Eight post-doctoral investigators have received grants from ANRF this year, including the second annual recipient of the James R. Klinenberg Memorial Fellowship, Wolfgang Hueber, M.D., of Stanford University School of Medicine. (Dr. Klinenberg was a world-renowned physican-researcher and past president of the American College of Rheumatology who passed away in December, 1999.)

The following is a brief description of the research being conducted by this year's grant recipients:

Wolfgang Hueber, M.D., Stanford University School of Medicine
Dr. Hueber will study a novel animal model of systemic lupus erythematosus (SLE or lupus), utilizing powerful new technology called protein microarray technique, to identify and characterize the immune response. This research holds great promise for detailing the immune response not only in lupus, but also in various other autoimmune diseases. Future studies based on Dr. Hueber's findings may identify a molecular target for development of a new therapy for lupus.

Mireille Delhase, Ph.D., University of California, San Diego Rheumatoid Arthritis (RA) is a common chronic inflammatory disease, characterized by joint inflammation and progressive cartilage destruction. This degenerative process is triggered by molecules, called cytokines, produced by cells from the immune system. Cytokines are responsible for activating a protein, which in turn induces the production of enzymes and molecules that amplify the inflammatory process. The enzyme responsible for protein activation by cytokines has recently been discovered. Dr. Delhase will study the molecular mechanism of this enzyme and identify potential new molecules involved in the initiation of the inflammatory process. The goal of this work is to develop new therapies to block inflammation in the early stage of RA before irreversible joint damage has occurred.

Michael Vincent, M.D., Ph.D., Brigham and Women's Hospital
Dr. Vincent will be studying the immune system at the molecular level. Specifically, he will identify the regulatory role of human T lymphocytes in the inflammatory process of arthritis, with the goal of defining potential targets for biologically specific therapies of autoimmune arthritis.

Sucheta M. Vaingankar, Ph.D., Veterans Medical Research Foundation (UCSD)
With aging and/or osteoarthritis, the cartilage in joints calcifies due to crystal deposits that directly provoke inflammation, pain and cartilage degeneration. The major mediator of these crystal deposits is a chemical inorganic pyrophosphate. Dr. Vaingankar's study is aimed at understanding the mechanism of the calcification of cartilage and may lead to the identification of novel pyrophosphate-based therapies for treating osteoarthritis.

Alla Tsytsykova, Ph.D., The Center for Blood Research (an affiliate of Harvard Medical School)
Tumor Necrosis Factor Alpha (TNF-alpha) is a protein responsible for inflammation and, ultimately, cartilage destruction in the joints of individuals with rheumatoid arthritis. Dr. Tsytsykova's project will study how the TNF-alpha gene is activated in T-lymphoctyes, the cells in the synovial fluid of joints that secrete TNF-alpha. The knowledge gained from this study may potentially lead to the development of therapies that interrupt TNF-alpha gene expression in RA.

Alan Stern, M.D., McGuire VA Medical Center
Hand Osteoarthritis (OA) is a very common form of osteoarthritis which has a genetic basis. Dr. Stern is conducting a clinical study of two hundred pairs of siblings affected by hand osteoarthritis. By analyzing the clinical and genetic information, this study will seek to define the potential inherited predisposition for hand OA. The search for potential genetic causes and influences for hand OA will likely precede important treatment advances.

Karen Costenbader, M.D., Brigham and Women's Hospital
Dr. Costenbader is conducting a randomized, double-blind study of 50 lupus patients to determine the appropriate dosing level of Pravastatin, an oral medication proven to reduce cholesterol levels in the general population. No studies have been done on pravastatin's effect on lupus patients or those receiving steroids. High cholesterol levels are common in lupus patients (at least partially resulting from their treatment with steroids). Establishing the doses of pravastatin necessary to reduce cholesterol in lupus patients will contribute to a strategy of comprehensive care for this high-risk group.

Xin Dong, Ph.D., University of Pittsburgh School of Medicine
More than 80 percent of rheumatoid arthritis patients produce antibodies against their own immune system, called rheumatoid factors. It is believed that rheumatoid factor production by B cells is controlled by specific "antibody-reactive" T cells. Dr. Dong is studying the T cells thought to produce rheumatoid factors. This work may lead to the design of drugs or therapeutic strategies to inhibit these specific T cells from producing autoantibodies.

The grant fellowships described above total more than $350,000. Since 1952, the Arthritis National Research Foundation has provided over $4 million for arthritis research. Based in Long Beach, California, ANRF disseminates information to the public on current research through a periodic newsletter and their web site, www.curearthritis.org. Fellowships are awarded on an annual basis. Proposals are peer-reviewed by the ANRF Scientific Advisory Board of Directors, nationally recognized expert scientists and physicians in the field.

For more information on the Arthritis National Research Foundation or a copy of the Grant Guidelines, contact:
Helene Belisle, Executive Director, Arthritis National Research Foundation, 200 Oceangate, Suite 400, Long Beach, CA 90802.
800-588-2873; 562-983-1410 (fax), or anrf@ix.netcom.com (e-mail). Internet web site: www.curearthritis.org

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