Stroke is the second most common cause of cardiovascular-related mortality after myocardial infarction. About 700,000 Americans suffer a new or recurrent stroke each year due to atherosclerosis in the carotid/vertebral arteries. Between 15-30% of victims are permanently disabled and 20% require institutional care. As a result, stroke is the most common cause of long-term serious disability in the US and represents an economic burden similar in scale to myocardial infarction. Clinical guidelines have largely restricted pharmaceutical options to measures that limit the development of ischemia (ie thrombolytics/anticoagulants); however the window of therapeutic opportunity is narrow (probably less than six hours) and the risk of side effects high. Hence thrombolytics are given to as few as 3% of patients who present with ischemic, non-hemorrhagic stroke. According to a market report published by Frost & Sullivan in 2001, the US market for all stroke therapies was around $1.4 billion in 2000. This report also predicted that improving clinical treatment options allowing therapies to reach the remaining 97% of patients could increase the market to more than $3.8 billion by 2007. Current pharmaceutical development efforts are diverse and include multiple potential targets. Some of these are described in a series of dossiers produced for ThromboGenics, one of the leaders in this field (click here for access). Inflammatory processes have been implicated in the pathogenesis of brain damage after stroke. In rodent stroke models, focal ischemia induces several proinflammatory chemokines, including monocyte chemoattractant protein-1 (MCP-1). The individual contribution to ischemic tissue damage, however, is largely unknown. To address this question, Novartis researchers subjected MCP-1-deficient mice (MCP-1-/-) to permanent middle cerebral artery occlusion (MCAO). This procedure produced similar cerebral perfusion deficits in wild type and MCP-1-/- mice, however infarcts were 29% smaller in the latter, a finding suggested to be related to reduced interleukin-1beta production and consequent tissue protection. The results of this study indicate that inhibition of MCP-1 signaling could be a new acute treatment approach to limit infarct size after stroke. Further studies are eagerly awaited to determine whether such molecules afford a better window of therapeutic opportunity and/or a reduced risk of hemorrhage than thrombolytics/anticoagulants in current use

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