Cosmic Implications of NXY-059

Abstract

The SAINT studies on NXY-0591,2 have reinvigorated debate over the momentous issues of neuroprotection and the development of novel stroke therapeutics. Some may argue there is little new ground that NXY-059 has unearthed and, in fact, the clinical trials merely confirm that as a strategy, neuroprotection has not been shown to be effective. Editorials in high-profile journals have sent out the clarion call to terminate research on neuroprotection given decades of work, which has uniformly led to failure after failure in clinical studies.3 These sentiments are premature and ignore studies showing that hypothermia improves outcome in patients after cardiac arrest, a major cause of global cerebral ischemia.4,5 Proof for the neuroprotection concept has therefore already been established. Despite decades of neutral clinical trials, there still remains optimism among the stroke academic community. A majority of university-affiliated stroke neurologists in the United States in a recent survey still believe neuroprotection is a viable therapeutic strategy, although admittedly, that survey was conducted between the SAINT I and SAINT II publications.6 However, the question whether neuroprotection will ever work in stroke has been overshadowed by the larger issue of whether animal studies, which serve as the foundation for the development of stroke therapeutics, are even relevant to our patients with acute stroke. In the discussion section of the SAINT II article, the authors write, “it is possible that the animal models of acute focal infarction are not relevant to the patient population; they certainly are insufficient to guarantee a positive clinical-trial result.” Have all prior neuroprotective agents failed in clinical studies because rodent stroke is not relevant to human stroke? This is a key question. Substantial reductions in infarct size in rodents with stroke treated with various types of purported neuroprotective agents would seem to support this view. There …