A drug called tPA has proven its value as the most effective emergency treatment for a common kind of stroke over the last decade. Its effectiveness is limited by two factors: tPA can cause dangerous bleeding in the brain and its brain-saving power fades fast after the third hour of a stroke.
A new paper published online in Nature Medicine reveals why tPA has these limitations. It also gives tantalizing evidence about how those problems might be overcome, if a stroke victim first takes a drug currently used to treat leukemia.
The researchers, from the University of Michigan and the Ludwig Institute for Cancer Research (LICR) Stockholm Branch at Karolinska Institutet emphasise that it's still too early to apply their findings from mice to the treatment of stroke victims everywhere.
A clinical trial will begin soon to test the theory in humans, using the leukemia drug imatinib (Gleevec). In mice, that drug greatly reduced bleeding, even if tPA wasn't given until five hours after a stroke began.
tPA apparently increases the risk of bleeding and leakage of fluid within the brain, by accident. The drug has a tendency to act upon a protein known as PDGF-CC, and the PDGF-alpha receptor that it binds to. This interaction causes the usually impervious "blood-brain barrier" to become porous, leading to leakage. Gleevec inhibits the PDGF-alpha receptor, potentially counteracting tPA's effect.
The trial results are awaited with anticipation... If these findings are confirmed in humans, Gleevec could be given immediately when a stroke is suspected to extend the window in which tPA may be given.
Tuesday, June 24, 2008
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