http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268079/
Abstract
Stroke
is a major cause of both death and disability. However, there are no
pharmacological treatments used in most countries other than recombinant
tissue plasminogen activator, a thrombolytic, and this is only used in
about 4% of patients presenting after an acute ischaemic stroke. One
novel thrombolytic (desmoteplase) has just been reported to have failed
in a Phase IIb/III trial, but other thrombolytics and reperfusion agents
remain in development. The picture with neuroprotectant agents, that is
compounds that act to preserve neurones following an acute cerebral
ischaemic insult, is even more bleak. Despite the development of over
1000 compounds, many proving effective in animal models of stroke, none
has demonstrated efficacy in patients in the over 100 clinical trials
conducted. This includes NXY-059, which was developed in accordance with
the guidelines proposed by an academic-industry roundtable group
(STAIR). This review examines the available data on compounds currently
in development. It also proposes that the failure of translation between
efficacy in preclinical models and patients is likely to terminate most
current neuroprotective drug development. It is suggested that animal
models must be made more representative of the patient condition (with
other co-morbid conditions) and suggests that since stroke is primarily a
cardiovascular disease with a neurological outcome, more research on
the neurovascular unit would be valuable. New approaches on
neuroinflammation, neurorestoration and neurorepair are also likely to
gain prominence in the search for new drugs to treat this major clinical
problem.
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