New research by Biogen (NASDAQ/BGEN) scientists published today in the journal Science offers important insights into the mechanism and possible treatment of autoimmune diseases. The studies present new information about BAFF (B cell activating factor of the TNF family), a protein central to normal B lymphocyte development. They also identify the receptor protein that is a key target for developing drugs to treat disorders associated with abnormal B lymphocyte activity, such as systemic lupus erythematosis (SLE) and rheumatoid arthritis (RA).
B cells are an important component of the immune system that produce antibodies, which attach to foreign matter and initiate the body’s self-defense response. Biogen scientists first published data establishing the link between BAFF and B lymphocyte function in 1999 and demonstrated that too much BAFF leads to lupus-like symptoms in mice by causing an increased number of B cells and B cell hyperactivity. More recently, it has been shown that many SLE and RA patients have higher than normal levels of BAFF circulating in their blood, suggesting that BAFF may play a role in human diseases.
The research reported today describes a new receptor protein for BAFF, called BAFF-R, and the consequences when mice lack either BAFF or BAFF-R. It demonstrates that both BAFF and BAFF-R are essential for normal B cell development and that mice that lack BAFF and mice that possess an abnormal form of BAFF-R have significantly reduced numbers of mature
B lymphocytes. As a result, their ability to generate antibody responses to foreign proteins is compromised. In contrast, mice lacking either of the BAFF receptors previously identified – BCMA and TACI – have largely normal numbers of B lymphocytes and normal or near normal antibody responses. The research thus identifies BAFF-R as the protein through which BAFF primarily acts. Based on these results, BAFF-R is likely to be an especially attractive receptor protein to target in drug development and treatment for diseases such as SLE that involve B cell abnormalities.
“We have established an important relationship between BAFF and BAFF-R in mice,” said Susan Kalled, Ph.D., Project Leader for Biogen’s BAFF program. “BAFF-R acts very specifically with BAFF, unlike the two previously identified receptors, which can bind to another protein molecule in addition to BAFF. Importantly, it appears that BAFF-R is the principal receptor for BAFF-mediated B cell survival in peripheral immune organs.”
The research published today was led by Biogen scientists Christine Ambrose, Ph.D., Jeffrey Thompson, B.S., and Martin Scott, M.D., Ph.D.
The papers will be posted beginning August 16, 2001 at www.sciencexpress.org.
Biogen, Inc., winner of the U.S. National Medal of Technology, is a biopharmaceutical
company principally engaged in discovering and developing drugs for human healthcare through genetic engineering. Headquartered in Cambridge, MA, the Company’s revenues are generated from international sales of AVONEX® (Interferon beta-1a) for treatment of relapsing forms of multiple sclerosis, and from the worldwide sales by licensees of a number of products, including alpha interferon and hepatitis B vaccines and diagnostic products. Biogen’s research and development activities are focused on novel products to treat inflammatory and autoimmune diseases, neurological diseases, cancer, fibrosis and congestive heart failure. The Company maintains active clinical research programs in protein therapeutics, small molecules, genomics and gene therapy. For copies of press releases and additional information about the Company, please consult Biogen’s Homepage on the World Wide Web at http://www.biogen.com.