Reports in Immunity and Journal of Clinical Investigation Implicate Key Protein in Development of Disease Affecting More Than One Million Americans

Biogen (NASDAQ: BGEN) announced today new research that points to novel strategies for treatment of inflammatory bowel diseases (IBD), a family of relapsing and tissue-destructive diseases that are associated with chronic inflammation of the intestinal tract, by targeting the expression of a protein known as alpha1 integrin and confirms the key role that the innate arm of the immune system plays in the development of these diseases. These discoveries also more broadly point to new fertile areas of inflammatory disease research, which to date has focused more on cells of the acquired versus the innate or “native” immune system. The discoveries are reported in recent issues of the journal Immunity and in The Journal of Clinical Investigation.

The studies were conducted by a team of Biogen scientists led by Antonin de Fougerolles, Ph.D. and Victor Koteliansky, Ph.D., M.D., and were performed in collaboration with Professor Neil Granger from Louisiana State University and Professor Stefano Fiorucci from University of Perugia, Italy.

The two major types of IBD are Crohn´s disease, which can affect any part of the digestive tract, and ulcerative colitis, which affects only the colon. There are more than one million cases of IBD in the United States alone, about equally divided between ulcerative colitis and Crohn´s disease.

The study authors investigated the role of alpha1 integrin in two different mouse models of inflammatory bowel disease. The scientists found that alpha1 integrin can be expressed on activated T-cells and monocytes during disease, and also that lack of alpha1 integrin or its blockade with a monoclonal antibody attenuated colitis. Monocytes and T-cells are white blood cells that play an important role in the initiation and mediation of immune and inflammatory responses. Development and alpha1-mediated inhibition of disease could occur independently of cells of the acquired immune system, thus pointing to the activated monocyte as a key alpha1-expressing cell type involved in the development of IBD.

“In inflammatory bowel diseases, it is largely within the gut that inflammatory responses are localized and perpetuated,” said Antonin de Fougerolles, Ph.D., Senior Scientist at Biogen. “This research demonstrates that interaction of leukocyte-associated alpha1 integrin receptors with the surrounding extracellular matrix plays a pivotal role in mediating intestinal inflammation in part via promotion of T-cell and monocyte movement and activation within the inflamed tissue. Novel therapeutic strategies, such as inhibition of alpha1 function, which disrupt matrix/leukocyte interactions may prove beneficial in treating intestinal inflammation.”

“We are very pleased to have been able to collaborate on these studies with outstanding academic investigators,” said Dr. Koteliansky, Director of Biological Research at Biogen. “Both studies serve to underscore the important role that cells of the innate immune system, such as monocytes, play in inflammatory disease. While much attention in inflammatory disease research has been centered on cells of the acquired or ‘specific’ immune system, we believe that the innate or ‘native’ immune system also plays a significant role.”

Unlike acquired immunity, innate immune responses require no prior exposure to infectious microbes or other foreign substances and do not discriminate among most foreign substances. When challenged, cells of the innate immune system are active from the start. Efforts to try to modulate this arm of the immune system hold great promise for the treatment of inflammatory and autoimmune disease.

Affected gut tissue in inflammatory bowel disease is characterized by dense infiltration of immune cell types (leukocytes), and therapeutic strategies to interfere with adhesion molecules necessary for migration and localization of leukocytes into tissues are under investigation. IBD accounts for 700,000 physician visits and 100,000 hospitalizations per year.

About Biogen

Biogen, Inc., winner of the U.S. National Medal of Technology, is a biotechnology 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 U.S. and worldwide 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

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