Another treatment landmark — for people with arthritis, for the UCSF Division of Rheumatology and for the Rosalind Russell Medical Research Center for Arthritis — was achieved when the FDA recently announced final approval of the new drug, Abatacept, for rheumatoid arthritis.
The pioneering laboratory research that led to the new biologic agent, which is also considered to hold substantial potential for treating lupus and other autoimmune diseases, was conducted at UCSF with strong financial support from the Rosalind Russell Center. "Every piece of the work we have done related to the development of Abatacept — as is true with so many of our research efforts — has received critical, ongoing funding from the Center," says Dr. David Wofsy, George A. Zimmermann Distinguished Professor of Rheumatology at UCSF, whose lab played a major role in the breakthrough.
The most recent major advance in treating RA was the introduction of the class of drugs known as "TNF" inhibitors — including Remicade, Enbrel and Humira — that specifically target inflammation and the joint destruction and pain it causes. However, as effective as these drugs are, they have not proven useful for about one-third of RA patients and do carry the risk of side effects.
Abatacept employs a different strategy, targeting the immune system rather than the inflammatory process. Clinical trials demonstrated that approximately two-thirds of RA patients using the treatment, usually in combination with methotrexate or another drug, experienced significant, sustained improvement in their disease. It is hoped that, with early use, Abatacept could help stop disease progression. The drug is also expected to be a useful alternative for patients for whom methotextrate and other therapies are not effective. Dr. Wofsy emphasizes, however, that Abatacept is not a cure. Ongoing treatment is required to continue to affect the disease.
Dr. Wofsy began working on this treatment strategy in 1992, underscoring the typically lengthy time required to develop a new drug and conduct clinical trials. The UCSF scientists built their investigation on findings in the late 1980s that a molecule on the surface of immune cells — dubbed CTLA4 — plays a key role in maintaining "tolerance," the process that permits the body to discern the difference between its cells and the outside world. In RA, systemic lupus and other rheumatic diseases, the failure of that process results in the body attacking itself.
Given the importance of CTLA4 in ensuring a functional immune system, Dr. Wofsy and others believed it might be possible to restore tolerance for people with autoimmune disease by creating a treatment that would mimic the molecule's structure and characteristics. The result was CTLA4Ig, now known as Abatacept.
"We hope that by restoring the body's tolerance process, we may have an effect not only on other forms of arthritis but also on such autoimmune diseases as diabetes and multiple sclerosis," Dr. Wofsy says. "Also, we expect this treatment approach will be safer, less toxic, than the potent immunosuppressive drugs used now because its effect on the immune system is more selective."
Today, the UCSF Arthritis Clinical Research Center — with support from the Rosalind Russell Center — is testing Abatacept in clinical trials as a treatment for lupus. "Our research program would be smaller, and the achievements far fewer, without the Center's commitment to our work," Dr. Wofsy comments.
(Published June 2006 in Arthritis Progress Report, the newsletter of the Rosalind Russell Medical Research Center for Arthritis. To be added to our mailing list, please send us a note with your name and address to
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"Every piece of work we have done related to Abatacept has received critical, ongoing funding from the Rosalind Russell Center."