Natalizumab: a new therapy for acute ischemic stroke?

Natalizumab, a well-characterized treatment for multiple sclerosis, is a humanized antibody against alpha-4 integrin (CD49d) that mitigates the transmigration of leukocytes across the endothelium. Although numerous experimental studies have evaluated the efficacy of anti-CD49d antibody treatment for ischemic stroke, discrepancies in their results have raised concerns about the benefits of this approach.

This article reviews the main experimental studies on the blockage of CD49d and identifies the potential underlying causes for their inconclusive results. Despite these divergences and the difficulties in translation of experimental studies, a phase II clinical trial has recently been conducted to evaluate the efficacy of natalizumab in stroke patients (ACTION trial). Preliminary results of the trial are also discussed here, together with a general overview of the emerged importance of the neuroprotective strategies based on the mitigation of post-stroke neuroinflammation. Expert commentary: Despite natalizumab showing positive effects on functional outcome similar to what was found in experimental models, a better understanding of how this happens without reducing the infarct volume requires further research. Therefore, new clinical trials are needed to confirm its neuroprotectant role in ischemic stroke.