Inhibition of alpha4 integrin to protect the brain against ischemic injury

The potential use of anti-alpha4 antibody presents an attractive approach to the treatment of stroke for a number of reasons: firstly, access to the site of action; alpha(4) is expressed on circulating leukocytes, permitting efficacy with systemic administration and negating the requirement for passage across the blood-brain barrier, an important consideration for neuroprotective and neurotrophic agents and other antiinflammatory approaches such as chemokine inhibitors. Pharmacokinetic studies in the rat have demonstrated a maintained pharmacological action of alpha(4) antibody for up to 72 hours after a single intravenous dose using leukocytosis as a surrogate marker for activity. Finally, the ubiquitous pattern of alpha(4) expression on different leukocyte subsets makes it an attractive target to combat the early and late inflammatory responses to brain injury.