Natalizumab: a new therapy for acute ischemic stroke?

ABSTRACT

Introduction: 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.

Areas covered: 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.

KEYWORDS:

• Stroke
• inflammation
• Natalizumab
• leukocyte infiltration
• neutrophils and T-lymphocytes
• alpha-4 integrin

Declaration of interest

Joan Montaner has received personal compensation from Biogen for serving as a national coordinator of the ACTION and ACTION 2 trials in Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Neurovascular Research Laboratory takes part in the Spanish stroke research network INVICTUS (RD12/0014/0005). A.Simats is supported by a predoctoral fellowship (2015 FI_B00952) from the Agència de Gestió d’Ajuts Universitaris I de Recerca (AGAUR).