A research paper published online in Nature Medicine has revealed shortcomings in the drug tPA, used as an emergency treatment to treat the most dangerous type of stroke.
According to research, although tPA has proven its worth, it can cause dangerous bleeding in the brain, and its effectiveness fades rapidly after the third hour following a stroke.
The study found that these problems can be overcome by using administering a drug used to treat leukaemia, first.
The researchers, from the University of Michigan in the US and the Ludwig Institute at the Karolinska Institutet in Stockholm, Sweden, have stressed that it is too early to apply their findings, carried out on mice, to the treatment of stroke victims generally.
They plan to initiate a clinical trial using imatinib (Glivec). In mice, imatinib greatly reduced bleeding, even when tPA was given five hours after the beginning of the stroke.
The researchers found that tPA appears to increase the risk of bleeding and fluid leakage within the brain. The drug has a tendency to act upon the PDGF-CC protein, and the PDGF-alpha receptor it binds to. This causes the blood–brain barrier to become porous, leading to leakage. Imatinib prevents this by inhibiting the PDGF-alpha receptor.
Ulf Eriksson, PhD, the leader of the team at the Ludwig Institute at the Karolinska Institutet, said: “Our research group identified the growth factor PDGF-CC ten years ago and we are now very excited having unraveled a mechanism in the brain involving this factor, which potentially will be a revolution in the treatment of stroke.
“Together with our clinical colleagues at the Karolinska University Hospital in Stockholm we are now rapidly continuing to explore this exciting possibility in clinical trials involving stroke patients.”