New Discovery Published in the Journal Immunity Has Important Implications for Finding New Approaches to Treating Immune and Inflammatory Diseases
A new discovery published today in the journal Immunity confirms that interactions between the extracellular matrix (ECM), which plays an important role in modifying cell behavior, and integrins, cell surface receptors that are responsible for interaction of cells within the ECM, can regulate gene expression. This discovery has important implications for finding new approaches to treating diseases characterized by inappropriate inflammatory and immune responses, such as atherosclerosis, rheumatoid arthritis, colitis and multiple sclerosis. The research was reported by a team of scientists from Biogen, Inc. (NASDAQ:BGEN), and CuraGen Corporation (NASDAQ:CRGN).
Several years ago, scientists postulated that the extracellular matrix (ECM) was a potent regulator of gene expression. This research is the first time this hypothesis has been demonstrated in a global, or genome-wide, comprehensive manner. The ECM-integrin pathway is of particular importance, because integrins are known to be desirable targets for therapeutic intervention and many new potential drug targets have been identified by identifying pathways and genes they induce.
The research was conducted by a team of Biogen scientists led by Victor E. Koteliansky, Ph.D., and Antonin R. de Fougerolles, Ph.D., who used a comprehensive and quantitative restriction enzyme-based profiling technique known as GeneCalling® to analyze differentially expressed genes. They discovered that ECM is a potent regulator of gene expression and confirmed for the first time that the degree of integrin-specific gene expression is considerable. GeneCalling is a patented gene expression technology developed by CuraGen Corporation.
Dr. Koteliansky and Dr. de Fougerolles said, “We are very excited about these discoveries. We have identified two pathways of gene transcription, confirmed the importance of ECM-integrin interactions in monocytes, and positively identified on a global and unbiased basis a large number of matrix-induced genes. These discoveries will help us to better understand how to interfere with cell-matrix interactions, as we continue to seek ways to develop small molecule and protein-based therapies to treat immune and inflammatory diseases.”
The research reported today analyzed and quantified the relative effect of ECM-integrin mediated cell attachment on monocyte gene expression, its regulation by growth factors and the integrin specificity of cell-ECM interaction. The team found that the adhesion of monocytes to extracellular matrix, potentiated by the presence of growth factors, resulted in the increased expression of numerous inflammatory and immune response genes. This finding revealed an important role for ECM-integrin interactions in affecting monocyte function and thus impacting on the development of disease pathologies. Identification of ECM-induced genes may also help in understanding the role of monocytes in disease.
Monocytes are large white blood cells that, during an inflammatory response, are recruited to the site of infection, often within ECM rich tissues, and undergo differentiation into macrophages. Macrophages are cells of the immune system that are present in almost every tissue. These cells play an essential role in the disposal of foreign agents and in the initiation and mediation of immune and inflammatory responses, as well as in the repair process following tissue injury.
In addition to historical information, this press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Reference is made in particular to statements regarding the potential implications of the new discovery. These statements are based on the Company’s current beliefs and expectations as to such future outcomes. Factors which could cause actual results to differ materially from the Company’s current expectations include the risk that further work in this area may change the Company’s view of the implications of the discovery. Reference is also made to the other risks and uncertainties described from time to time in the Company’s periodic reports filed with the Securities and Exchange Commission.
This research was conducted in collaboration with CuraGen Corporation, using its proprietary GeneCalling technology. CuraGen Corporation is advancing the discovery and development of pharmaceutical and life science products through the systematic application of genomics. CuraGen’s fully integrated, Internet-based functional genomic technologies are designed to rapidly generate comprehensive information about genes, human genetic variations, gene expression, protein expression, protein pathways, and potential drugs that affect these pathways. The Company is applying this comprehensive functional genomic platform to develop protein and antibody drugs, and to identify small molecule drug targets. CuraGen has conducted research for collaborators including Abgenix, Biogen, COR Therapeutics, Dupont/Pioneer Hi-Bred International, Gemini Genomics, Genentech, Glaxo Wellcome, Hoffmann-La Roche, Ono Pharmaceuticals, and Roche Vitamins. CuraGen employs over 325 people and is headquartered in New Haven, CT. Additional Company information is available at www.curagen.com.
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 ( Prescribing Information ). Biogen’ 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.