The goal is to demonstrate that blocking an adhesion receptor involved in inflammation (i.e., the integrin VLA-4) has a therapeutic benefit in chronic inflammatory disease. Specifically we propose to assess efficacy of anti-adhesion treatment by looking oat three parameters: leukocyte infiltration, expression of inflammatory markers and accumulation of extracellular matrix. Chronic inflammatory diseases (e.g., asthma, rheumatoid arthritis, psoriasis, restenosis and multiple sclerosis) pose a major healthcare challenge in the United States and worldwide. To provide a frame of reference, asthma alone affects approximately 10 million people in the U.S. population and it is estimated that $4 billion is spent annually on asthma care. While inflammation constitutes a common denominator to all chronic diseases described above, targeting adhesion molecules to prevent recruitment and infiltration of inflammatory leukocytes is a relatively new therapeutic approach. Consequently, the proposed research could have a major impact in the clinical management of human chronic disease.
The top priority of the proposed research is to assess efficacy of VLA-4 integrin blockade as a mode of therapy. In addition, we will be evaluating small molecule VLA-4 blockers which could then be potentially appropriate for chronic administration. Consequently, successful demonstration of in vivo use should translate into straightforward application to treat chronic inflammatory disease.
