Development of the Nitrone‐Based Spin Trap Agent NXY‐059 to Treat Acute Ischemic Stroke

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Abstract
The only current FDA‐approved treatment for acute ischemic stroke is thrombolysis with tissue plasminogen activator (tPA). However, there are numerous shortcomings to tPA treatment including an increased incidence of intracerebral hemorrhage (ICH) and a short therapeutic window (3–6 h). In recent years, studies have attempted to identify new therapeutics that might be neuroprotective following ischemic strokes. Free radical scavenging spin trap agents have been proposed as potential candidates for stroke therapy because of the hypothesized role of free radicals in the progression of stroke and ischemia‐induced neurodegeneration. Novel spin trap agents like (disodium‐[(tert‐butylimino) methy1] benzene‐1,3‐disulfonate N‐oxide (NXY‐059) are of particular interest, not only because they are broad‐spectrum nitrone‐based free radical scavengers, but also because of their safety profile in humans. Moreover, the rationale for developing NXY‐059 for the treatment of acute ischemic stroke is further supported by the drug's reported neuroprotective effects. In addition, NXY‐059 may represent a useful adjunct stroke therapy to tPA, since preclinical studies have demonstrated that NXY‐059 increases the therapeutic window for tPA and lowers the occurrence of tPA‐induced ICH.

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