Krembil scientists develop lab study to accurately predict outcomes of stroke neuroprotectant

Published on October 4, 2012 at 8:08 AM · No Comments

Scientists at the Krembil Neuroscience Centre, located at the Toronto Western Hospital, University Health Network have developed the first lab study in the world to accurately predict the outcomes of a human clinical for their drug that protects the brain against the damaging effects of stroke.

The study, "A translational paradigm for the preclinical evaluation of the stroke neuroprotectant Tat-NR2B9c in gyrencephalic non-human primates", published online today in Science Translational Medicine was conducted concurrently with a human clinical trial called ENACT. The purpose of the animal study was to test whether the Toronto team could predict benefits of the stroke drug Tat-NR2B9c in a larger, multi-center trial conducted in humans. This study builds on work previous published in the journal Nature earlier this year, which showed the ability of this drug to reduce brain damage caused by stroke.

Several previous attempts at developing stroke drugs have suggested that certain drugs were effective in reducing stroke damage in small animals such as rats. However, none have shown efficacy in patients suffering from stroke, leaving an unexplained gap between results of studies in animals and those in humans. The landmark research conducted by the Toronto team provides the first path forward in enabling researchers to predict whether or not a drug may work in humans. The UHN scientific team ran a trial in the lab that mimicked the design of a human clinical trial, which was conducted across Canada and the USA.

Both studies evaluated the effectiveness of Tat-NR2B9c when it was administered after the onset of embolic strokes. The laboratory study replicated in animals the small strokes that are incurred by patients who undergo neurointerventional procedures to repair brain aneurysms. This type of small ischemic stroke, which was simulated in a lab setting, occurs in over 90% of aneurysm patients after such a procedure, but usually does not cause overt neurological disability.

In the research lab, animals were randomized to receive either Tat-NR2B9c or placebo. Those treated with Tat-NR2B9c showed a marked reduction in both the numbers and the volumes of strokes when compared with the placebo group.

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