April 23, 2002

NIH-Funded UCSD Rheumatic Diseases Center
To Facilitate Collaboration, Speed Discoveries

The University of California, San Diego (UCSD) School of Medicine has received a 5-year, $3 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases for a Rheumatic Diseases Core Center (RDCC) designed to speed up the development of new diagnostic tools and therapies for the millions of individuals suffering from rheumatic diseases.

At a recent RDCC retreat, Drs. Gary Firestein, left, and Gregg Silverman, right, met with more than 40 scientists from UCSD, The Scripps Research Institute, La Jolla Institute of Allergy and Immunology, the Salk Institute for Biological Studies, and local biotechnology companies.  The researchers discussed collaborative efforts and the new services available from the RDCC.

The RDCC makes advanced scientific tools available to researchers and offers opportunities for collaboration between investigators from the host UCSD campus and two affiliated institutions, The Scripps Research Institute and the La Jolla Institute for Allergy and Immunology. Researchers from 30 laboratories will participate in the RDCC program, with additional collaborations anticipated with the Salk Institute of Biological Studies and area biotech companies.

RDCC director and UCSD associate professor of medicine Gregg Silverman, M.D., said the goal of the RDCC is translational medicine, the rapid movement of innovative scientific discoveries from the laboratory to patient treatment.

"We'll be successful if during the next five years we're able to develop new diagnostic tests and undertake several new clinical trials of innovative therapies," he noted.

Rheumatic diseases, which include arthritis, fibromyalgia, systemic lupus erythematosus (SLE), scleroderma, gout and other ailments, affect more than 40 million Americans. Symptoms include pain, stiffness and swelling in joints and other supporting structures of the body such as muscles, tendons, ligaments and bones. Many rheumatic diseases can also affect internal organs.

The cause of most rheumatic diseases is still under investigation and early diagnosis is difficult. Treatment varies depending upon the specific disease, but frequently includes rest and relaxation, exercise, proper diet, medication, surgery, and assistive devices such as splints or braces.

Among those attending the recent RDCC retreat were, left to right, Drs. Mitch Kronenberg, La Jolla Institute of Allergy and Immunology; Joel Buxbaum, Department of Molecular and Experimental Medicine, The Scripps Research Institute; Gregg Silverman, UCSD; and Toshiaki (Toshi) Kawakami, La Jolla Institute for Allergy and Immunology.

The RDCC will assist with several projects. One example is a local Phase 1 clinical trial of gene therapy approaches in the treatment of rheumatoid arthritis. This trial is the result of ongoing research by Gary Firestein, M.D., professor of medicine and chief, Division of Rheumatology, Allergy and Immunology, and Arthur Kavanaugh, M.D., associate professor of medicine and director, UCSD Center for Innovative Therapy.

In work already initiated, several personnel in the RDCC are working closely with Hal M. Hoffman, M.D., assistant professor of medicine and pediatrics, to better understand the genetic and molecular basis for an inherited chronic disease that is the cause of severe skin disease and often disabling arthritis. These studies have already led to insights into how a previously unknown human protein, expressed in white cells and normally involved in the defense of infection, connect different components of the immune system and contribute to the maintenance of cellular regulation.

RDCC resources also will greatly amplify the efforts of Silverman's research group that seeks to develop compounds based on the properties of natural bacterial toxins. They are working to develop related proteins to target the diseased B lymphocytes that are responsible for destruction of platelets and other cells in the body that occurs in patients with autoimmune diseases such as lupus.

"Two aspects of our program will speed the translation of scientific research into new treatment for patients," Silverman said. "With retreats, seminars and forums, we'll bring together a diverse group of scientists who have overlapping interests, but who might not otherwise interact and share information. UCSD will serve as the coordinating center to support, encourage and expand these interactions."

He added that the RDCC will also provide centralized, shared facilities:

  • A Molecular Biology Core, which provides specialized services such as DNA sequencing and antibody production;

  • A Biomarker Core, which offers specialized support in RNA and protein analyses for biomarkers, which are endpoints used to evaluate the immune response at molecular and tissue levels in animal models and patients with rheumatic diseases; and

  • An Animal Genetics Core, which develops strains of genetically manipulated mice, which are used to investigate the causes and progression of disease, as well as the potential of new therapies.

The UCSD program is one of seven RDCCs in the U.S. funded by the federal government.

Silverman noted that "the formation of these centers came from a realization at the federal level that a gap existed in resources available for fundamental research that could be translated into new diagnostic and therapeutic approaches. There was a presumption that industry, specifically pharmaceutical companies, would fund the research and conduct all the clinical trials of new medical therapies. However, research on rheumatic diseases, and in particular those which incorporate the latest technologic approaches, have not been the highest priority for drug companies."

He added that the funding allows UCSD and area researchers to investigate high risk, innovative approaches that might not otherwise be undertaken.

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The following are among the many researchers and projects in the RDCC:

  • Salvatore Albani, M.D., UCSD associate professor of pediatrics, studies genetic and environmental factors that influence rheumatoid arthritis. In addition, he plans a clinical trial of a new oral therapy for the disease.
  • Dennis Carson, M.D., UCSD professor of medicine and director, UCSD Sam and Rose Stein Institute on Aging, also directs an NIH-funded Specialized Centers of Research (SCOR) program on rheumatoid arthritis. An internationally recognized investigator in the field, he looks at new drug and genetic therapies to treat and prevent arthritis and cancer.
  • Edward Chan, Ph.D., The Scripps Research Institute, heads the DNA sequencing facility of the RDCC Molecular Biology Core. He studies autoantigens and autoantibodies in systemic autoimmune diseases and cancer, with the hope of understanding why specific large antigens are produced in various disease states.
  • Mary P. Corr, M.D., UCSD assistant professor of medicine, works on the development of a DNA vaccine for the treatment of inflammatory arthritis. In addition, she investigates the influence of antigen presentation on the immune response and has generated several transgenic animals for studies of B cell response and regulation.
  • Michael Croft, Ph.D., La Jolla Institute for Allergy and Immunology, is studying the role of CD4 T cells and cytokines in an animal model of rheumatoid arthritis. He is interested in cell signaling in allergic inflammation and the costimulatory interactions during the aging process.
  • Gary Firestein, M.D., UCSD professor of medicine and chief, UCSD Division of Rheumatology, Allergy and Immunology, brings his UCSD Center for Innovative Therapy to the RDCC as well as research into the origin and development of rheumatoid arthritis. His work has been instrumental in identifying the disease-associated cytokine networks, which are key components of the rheumatoid arthritis synovial inflammation process. In addition, his studies have identified proteins like TNF alpha as potential therapeutic targets.
  • Douglas R. Green, Ph.D., La Jolla Institute for Allergy and Immunology, studies the mechanisms of apoptosis (cell death) in the immune system, including its role in chronic rheumatoid arthritis and stress-induced apoptosis in T cells.
  • Arthur Kavanaugh, M.D., associate professor of medicine and director, UCSD Center for Innovative Therapy, is a nationally recognized leader in the design and conduct of clinical trials of novel therapies for patients with rheumatic diseases. He is also the clinical director of the RDCC.
  • Martin Lotz, M.D., chief, Division of Arthritis Research, The Scripps Research Institute, is internationally known for his investigations of osteoarthritis and the regulation of cartilage cells. He has been a leader in the development of new investigative approaches to understand cellular regulation of cartilage growth and metabolism, and his studies have made seminal contributions to understanding why cartilage wears out in individuals who may have an inherited predisposition for the development of osteoarthritis.
  • Eyal Raz, M.D., UCSD associate professor of medicine, investigates DNA vaccines for the treatment of allergic diseases. His studies have provided a foundation for feasibility studies and the use of DNA vaccination for the treatment of inflammatory arthritis.

Media Contact:
Sue Pondrom

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