VLA-4 antagonists

Evidence has accumulated over recent years for an important role for VLA-4 in inflammatory disease. Work with antibodies directed against VLA-4 or its primarily ligand VCAM-1 and peptides that mimic the Leu-Asp-Val (LDV) VLA-4 binding epitope on fibronectin suggest that asthma, rheumatoid arthritis, multiple sclerosis, atherosclerosis and inflammatory bowel disease are amenable to treatment with a VLA-4 antagonist. Several types of molecules, including humanised monoclonal antibodies, VCAM antisense polynucleotides, peptide mimetics of the LDV sequence and 4-substituted N-acylphenylalanine derivatives, constitute the major compound classes currently under development. Clinical trials with several compounds are underway with early reports of efficacy with the monoclonal antibody natalizumab in multiple sclerosis and Crohn's disease.