The individual members of ANRF's Scientific Advisory Board have committed their expertise to furthering the principles and goals of our organization on a regular basis. These scientists believe that ANRF plays a critical role in the field of rheumatic disease research: the Foundation funds young investigators, often giving them a “jump start” on their research careers. The Advisory Board members will be reviewing the grant proposals received by ANRF each year and recommend grant recipients, as well as providing advice to the Board of Directors on the trends in research and clinical treatments. The Scientific Advisory Board will be instrumental in implementing the organization's goal of funding more research projects each year. Their collective presence takes ANRF to a higher level of respect and prestige in the world of medical research.

Meet the Scientific Advisory Board

John H. Vaughan, M.D., University of California, San Diego
Dr. Vaughan is a past president of the American College of Rheumatology and has been studying the pathogenesis of rheumatoid arthritis throughout his career. A graduate of Harvard Medical School, Dr. Vaughan has directed the Immunology and Infectious Diseases Unit of the University of Rochester Medical School (1963-70), chaired the Clinical Research Department and the Clinical Immunology Department at Scripps Research Institute (1970-1989), and has been a Professor of Medicine at the University of California, San Diego since 1990.

Dr. Vaughan's career has been in teaching and research in the areas of allergy and the autoimmune diseases, such as rheumatoid arthritis. His major research contributions have been in elucidating the nature and significance of autoantibodies, early studies on the nature of cellular immunity, and more recent explorations of the probable contribution of virus infection in the autoimmune diseases. Dr. Vaughan is a former grant recipient of ANRF.

James Klinenberg, M.D., Cedars-Sinai Medical Center, Los Angeles
Dr. Klinenberg has served as president of the American College of Rheumatology and is currently Professor of Medicine and Assistant Dean of the UCLA School of Medicine. He earned his M.D. from the George Washington School of Medicine in 1959; his undergraduate and M.A. work was completed at Johns Hopkins University.

In addition to the American College of Rheumatology presidency, Dr. Klinenberg has held numerous positions of leadership in education, research and professional organizations, including the Association of American Medical Colleges, American College of Physicians, California Biomedical Research Association, local and national Arthritis Foundation, and Cedars-Sinai Medical Center. His research throughout most of his career has focused on the causes and mechanisms of rheumatic diseases, with an emphasis on the autoimmune diseases of lupus and rheumatoid arthritis.

Hugh McDevitt, M.D., Stanford University Medical Center
Dr. McDevitt is known world-wide for his contributions to the field of arthritis research. He is currently a professor of Mediciine, and Microbiology & Immunology at the Stanford University School of Medicine. A 1955 graduate of Harvard University Medical School, Dr. McDevitt has received honors and awards for his research- related work from academic and professional organizations ranging from the National Institutes of Health to the National Cancer Institute to the American College of Rheumatology, and more.

He currently serves on the Advisory Committee to the Director of the National Institutes of Health, as well as on the editorial boards of the publications, Molecular Medicine and The Journal of Clinical Immunology, Immunopathology, Immunogenetics. At Stanford University, Dr. McDevitt has been the head of the Immunology Department, the director of the Clinical Immunology Lab, and the Chairman of the Department of Microbiology and Immunology.

Grete Sonderstrup, M.D., Stanford University Medical Center
Dr. Sonderstrup is an Assistant Professor of Medicine in the Division of Immunology and Rheumatology at Stanford University Medical Center. She earned her M.D. from the University of Copenhagen in 1974, coming to the U.S. in 1986 to continue her research in immunology. Dr. Sonderstrup is a speaker in high demand, having been invited to universities and conferences all over the world to discuss her research work in rheumatoid arthritis. ANRF provided funding for Dr. Sonderstrup¹s work in 1993.

Eng M. Tan, M.D., Scripps Research Institute
Dr. Tan is Professor and Head of the Autoimmune Disease Center at the Scripps Research Institute in La Jolla, CA. He earned his M.D. degree from Johns Hopkins University in 1956. After his medical internship and residency, Dr. Tan began his post-doctoral research at Case Western Reserve University in Cleveland, then Rockefeller University in New York. He joined the Scripps Clinic and Research Foundation in 1967, and was head of the Department of Allergy & Immunology from 1970 to 1977. Since 1982, Dr. Tan has been head of the W.M. Keck Autoimmune Disease Center, where his work has centered on studies of autoantigens and autoantibodies in systemic rheumatic diseases and cancer.

Dr. Tan is a past president of the American Rheumatism Association, and has served on numerous advisory boards and research committees for the National Institutes of Health and various national scientific and medical organizations. In recognition of his achievement in this research field, Dr. Tan has received awards from organizations worldwide.

Carl F. Ware, Ph.D., La Jolla Institute for Allergy and Immunology
Dr. Ware received his Ph.D. from the University of California, Irvine in Molecular Biology and Biochemistry in 1979. He did his postdoctoral research at the University of Texas, Health Science Center, San Antonio, the Dana-Farber Cancer Institute in Boston, and the Department of Microbiology and Molecular Genetics at Harvard Medical School. Dr. Ware joined the La Jolla Institute for Allergy and Immunology (LIAI) in 1996 as Head and Member of the Division of Molecular Immunology and is also currently Adjunct Professor of Biology at the University of California, San Diego.

A major goal of LIAI's projects in Molecular Immunology is to understand how lymphotoxins and TNF, and newly discovered proteins induce cell death and growth, and to research the underlying factors that regulate the human immune system. Dr. Ware is considered an expert in the field of molecular immunology.

The 1998-1999 grant recipients represent the best and brightest young scientists seeking to understand the nature and cause of arthritis. Most of these studies center around the autoimmune diseases of rheumatoid arthritis (RA) and Systemic Lupus Erythematosus (SLE or lupus). In autoimmune disease, the patient's immune system is attacking and destroying self-tissues. By studying the causes of these diseases, scientists will be able to devise new therapies to fight them at the cell level. In fact, we are beginning to see disease-modifying therapies, not just anti-inflammatory drugs to help control pain.

One such new therapy for rheumatoid arthritis is a drug called “Enbrel,” which recently received FDA approval. The drug has been developed by the Immunex Corporation and has been tested in clinical trials across the country. Enbrel is a protein-based drug comprising only human amino acid sequences; in other words, substances already produced in the human body. The drug inhibits TNF (tumor necrosis factor) biological activity. In RA, excess TNF combines with cell-surface TNF receptors to produce a cascade of damaging and inflammatory effects on joints. Enbrel is thought to interfere specifically with the inflammatory process in RA, which is believed to be driven by TNF. (See page 5 for more information on Enbrel.)

ANRF is proud of the research it funded in the 1970's and 1980's which led to the original discovery of TNF, the target of these new therapies.

The Scientific Advisory Board adds a new dimension to the scope and prestige of the Arthritis National Research Foundation. The collective expertise of these renowned scientists and physicians will help the Foundation expand its influence into the next century. The Board of Directors is indeed grateful for their commitment to the Foundation's goals: helping young investigators study the basic science of rheumatic diseases in an effort to develop new therapies and, ultimately, a cure.

Thank you for your generous support of arthritis research as we work together toward improving the quality of life for those in pain.

Gale A. Granger,Ph.D.
President

Financial Report
Audited Statement of Public Support
Fiscal Year Ending March 31, 1998

“Understanding the disease pathway is the first step toward determining the cause of the disease and, ultimately develop new therapies,” said Gale A. Granger, Ph.D., Arthritis National Research Foundation president and Professor of Immunology at the University of California, Irvine. “The four investigators receiving grants from ANRF this year exemplify the Foundation¹s dedication to studying why and how the body reacts as it does in the pathogenesis of these autoimmune diseases.”

A normally functioning immune system enables us to recover from infections by releasing antibodies to attack foreign, unwanted substances. In Rheumatoid Arthritis (RA) and Lupus, which are autoimmune diseases, this highly efficient immune system has made a mistake and is attacking “self tissues.” While not the most prevalent form of arthritis (osteoarthritis impacts over 17 million Americans), RA and Lupus are the most painful and crippling rheumatic diseases, affecting nearly eight million Americans.

The investigators awarded grants for the 1998-99 grant cycle are:

Susan Kovats, Ph.D., Beckman Research Institute, City of Hope
Elizabeth Mellins, M.D., Stanford University Medical Center
Rebecca Tuetken, M.D., Ph.D., University of Iowa
Paul Utz, M.D., Harvard Medical School, Brigham & Women’s Hospital

Susan Kovats, Ph.D., of the Beckman Research Institute at City of Hope in Duarte, California, received a $35,000 grant to study the nature of self-antigens (substances released by the body, as opposed to foreign substances, to stimulate production of antibodies) in Rheumatoid Arthritis. Her investigation will focus on whether tissue damage or infection confuse the recognition mechanism of the immune system, thereby attacking self-tissues as if they were foreign. “Insights to these self-antigens will aid the design of strategies for therapeutic intervention in RA,” said Dr. Kovats. Dr. Kovats received her Ph.D. from the University of Wisconsin in 1991, and is currently an Assistant Research Scientist in the Beckman Institute's Division of Immunology.

Elizabeth Mellins, M.D., at Stanford University Medical Center, received $40,000 to test the hypothesis that RA susceptible genes interact differently with key regulators in the RA disease pathway than do non-susceptible genes. Specifically, she will investigate if inherited genetic alterations in the recognition mechanism of the immune system are defective and cause the patient to identify certain self-antigens as foreign. This novel approach may yield insight into RA pathogenesis, providing fuel for new therapeutic strategies. Dr. Mellins is a practicing pediatric rheumatologist and an innovator in the field of antigen presentation. She received her M.D. from Harvard Medical School in 1978 and has taught both Pediatrics and Rheumatology at the University of Washington, University of Pennsylvania and Stanford University Medical Center.

Rebecca Tuetken, M.D., Ph.D., at the University of Iowa, received $40,000 to study the mechanism of how the immune system recognizes and reacts against foreign and self-DNA (genetic information). This will help explain how certain patients with autoimmune diseases react against their own DNA. “My hope is that this study will provide both a more complete understanding of the innate immune response to bacterial DNA and new insights in the pathogenesis of SLE, possibly leading to new therapeutic approaches,” said Dr. Tuetken. Currently a post-doctoral fellow in Rheumatology at the University of Iowa Hospitals and Clinics, Dr. Tuetken received her Ph.D. in Immunology and M.D. from the University of Chicago Pritzker School of Medicine in 1989 and 1991, respectively.

Paul Utz, M.D., at Brigham and Women's Hospital (affiliated with Harvard Medical School) in Boston, received $40,000 to study cell death's role in the development of autoimmune diseases such as lupus and scleroderma. Dr. Utz's study will focus on the mechanism of how proteins released from dying self-cells can be modified and how these modified proteins then stimulate the patient's immune system. Once stimulated, the immune system will attack both dying and living cells to cause autoimmune disease.

Successful completion of this project may greatly advance the level of understanding of autoimmune disease mechanism. Dr. Utz is a practicing rheumatologist and instructor at Brigham and Women's Hospital and Harvard Medical School, who received his M.D. in 1991 from Stanford University School of Medicine.

Grants are awarded on an annual basis. Proposals are peer-reviewed by the Medical Committee of the Board of Directors, as well as by the Scientific Advisory Board, which comprises NIH-level expert scientists and physicians in the field.

Enbrel: The Long-Awaited TNF Inhibitor is Available
The FDA recently licensed a genetically engineered protein that helps reduce symptoms of moderate to severe, active Rheumatoid Arthritis (RA). RA affects over two million Americans and is an autoimmune disease in which the body attacks self-tissues. The new treatment, called Enbrel, binds to the tumor necrosis factor (TNF), a naturally occurring protein in the body, and inhibits its action. TNF, which is believed to promote inflammation in the body, is found at elevated levels in the fluid surrounding the affected joints of RA patients. This is the breakthrough treatment referred to in the lead article of the last issue of CureArthritis. Now that the FDA has approved this treatment, Enbrel injections will be available through your physician.

Enbrel is an entirely new approach to the management of RA. It is the first in a new class of drugs known as biologic response modifiers, which specifically interrupt the inflammatory process. In clinical studies, patients taking Enbrel had significantly reduced pain and the number of swollen and tender joints. The drug is intended for those RA patients with moderate to severe RA who have not been able to achieve relief with one or more disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate. It may also be used in combination with methotrexate. Known side effects are: Mild to moderate injection site reactions. The long-term effects, on the development or course of serious infection, malignancy and autoimmune disease are unknown. Patients with a serious infection, or who are allergic to Enbrel or any of its components should not take this medicine.

For more information, please consult your physician, call the Immunex Corporation at 1-888-4ENBREL, or visit the company-sponsored web site at  www.Enbrelinfo.com.

Arava approved for RA Treatment
In September, the FDA approved Arava (leflunomide) as a new treatment for adult RA. This drug, which is taken in tablet form, inhibits at least one enzyme in lymphocytes (cells of the immune system) and thereby interferes with the RA disease process. In clinical trials, patients taking Arava showed significant improvement in pain and swelling of joints and joint damage seemed to be retarded. Known side effects are: Not recommended for patients with significant liver disease, children, pregnant or nursing women. Patients may experience diarrhea or, rarely, liver problems, hair loss, skin rash or hypertension.

Still in the FDA pipeline
Cox-2 Inhibitors: Pain Relief without Stomach Upset
As many as 107,000 hospitalizations and 16,500 deaths occur each year in the United States as a result of the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen and aspirin. These drugs help pain management of arthritis, but patients may develop moderate to severe gastrointestinal problems. One solution may be on the way. A new class of drugs is being developed by Searle, and also by Merck & Co. These drugs are known as COX-2 inhibitors and are aimed at reducing the adverse effects on the gastrointestinal system. The preliminary results are promising: the drugs seem to target the COX-2 enzyme, produced primarily at the site of inflammation, while not inhibiting the COX-1 enzyme, which is needed for proper digestive function. It is the inhibition of COX-1, which is believed to be the cause of serious gastro-intestinal side effects, such as ulcers, which have been associated with the use of NSAIDs.

The review of Searle’s Celebrex (celcoxib) is on the fast track at the FDA. The drug is still in the testing phase at this time. You can visit Searle at their web site to obtain current information: www.searlehealthnet.com. Vioxx is the Cox-2 inhibitor drug which Merck & Co. is currently testing.

Non-Drug Treatment Alternative: Prosorba Column
The FDA Gastroenterology and Urology Device Advisory Panel recommended approval for the treatment of moderate to severe rheumatoid arthritis of Prosorba Column. This treatment has been used to treat Idiopathic Thrombocytopenic Purpura (ITP), an immune blood disorder, since 1987. If final approval from the FDA is received, Prosorba Column would also be used to treat RA.

Prosorba Column is a treatment similar to kidney dialysis, in which blood is removed from the patient's arm and passed through a machine that separates the blood cells from the plasma. The plasma is then passed through the Prosorba Column, recombined with the blood cells and finally returned to the patient through the other arm.

In clinical trials across the country, patients who had failed with DMARDs (such as methotrexate) underwent 12 Prosorba Column treatments. Nearly half of these patients showed significant reduction in swollen and tender joint counts and the response was durable, some lasting as long as 75 weeks.

Molina Medical Centers

Reed, Conner & Birdwell

For more information or to receive an invitation, please call 800-588-CURE.
Golf Chair: Jim Rose, Pharm.D.
ANRF Board Member