Research Article: Where Will the Next Generation of Stroke Treatments Come From?

Date Published: March 2, 2010

Publisher: Public Library of Science

Author(s): D. W. Howells, G. A. Donnan

Abstract: David Howells and G. A. Donnan discuss the next generation of stroke treatments and say that novel therapeutic targets may emerge from the stimulation of neuroplasticity and unraveling the genetic code of stroke heterogeneity.

Partial Text: Stroke, about 80% of which is ischaemic caused by occlusion of an intracerebral artery and 20% caused by intracerebral bleeding, is the second most common cause of death and disability globally. WHO statistics indicate that stroke and other cerebrovascular diseases kill approximately 5.7 million people each year. In the United States alone it is estimated that the 780,000 symptomatic strokes detected each year may be accompanied by a further 11 million asymptomatic strokes [1]. The need to reduce this burden by better use of existing therapies and identification of new ones is pressing.

Although a number of avenues of research may bring rewards in terms of completely new classes of intervention for the prevention and treatment of stroke, we believe two areas are most likely to generate completely new classes of therapeutic targets.

Remarkable progress has occurred over the last two decades in stroke interventions. Many have been developed on the basis of their efficacy in other disorders. This “inheritance” approach should continue, but two areas where completely novel therapeutic targets might emerge are the stimulation of neuroplasticity and unraveling the genetic code of stroke heterogeneity (Table 2). For the former, the next steps are to identify small-molecule, nontoxic compounds that most effectively enhance plasticity in animal models, and then subject them to clinical trial in humans. For the latter, more and larger-scale cooperative GWASs in carefully phenotyped stroke populations are required to better understand the polygenic nature of cerebrovascular disease. Then, the physiological relevance of genetic abnormalities can be determined in in vitro and in vivo systems before candidate compounds are developed.



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