The continued failure in approving new drugs for treatment of acute stroke has 
been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY 
Treatment (SAINT) II) trial. The disappointment was heightened by the latter 
study being viewed as a most promising compound for stroke drug development 
program based on the preclinical data. Since the SAINT I/II development program 
included many of the STAIR (Stroke Therapy Academic Industry Round table) 
guidelines, yet have still failed to achieve the expected efficacy, there is a 
clear need to continue and analyze the path forward for stroke drug discovery. 
To this end, this review calls for a consortium approach including academia, 
government (FDA/NIH), and pharmaceutical industry partnerships to define this 
path. It is also imperative that more attention is given to the evolving 
discipline of Translational Medicine. A key issue in this respect is the need to 
devote more attention to the characteristics of the drug candidate nature-target 
interaction, and its relationship to pharmacodynamic treatment end points. It is 
equally important that efforts are spent to prove that phenotypic outcomes are 
linked to the purported mechanism of action of the compound. Development of 
technologies that allows a better assessment of these parameters, especially in 
in vivo models are paramount. Finally, rational patient selection and new 
outcome scales tailored in an adaptive design model must be evaluated.