Researchers at the University of Oslo are proposing a novel treatment for stroke that involves administering an infusion of a blood protein suspected to protect the brain from damage. Early tests in mice indicate if the treatment is given within hours of a stroke occurring it could improve long-term outcomes.
"Those who survive [a stroke], often sustain life-changing brain damage," explained Sandip Kanse, one of the authors on the new study. "In addition to the cost in human suffering, caring for these patients is very expensive for health care systems. It is therefore important that we find treatments that can be applied immediately after a stroke. For every minute that is lost, more of the brain is damaged."
The study focused on a circulating blood protein called factor VII activating protease (FSAP). This protein has long been linked to stroke, with research showing levels of it increase in the bloodstream following a stroke. And, people with a gene mutation that reduces their FSAP levels are often at a higher risk of suffering from stroke.
So the hypothesis was that FSAP somewhat protects the brain from the harmful effects of stroke, and maybe it could be turned into a treatment. The first step was looking at what happens to mice when a stroke is induced but FSAP-production is completely inhibited.
"The mice that had had their FSAP gene removed suffered more brain damage than the normal mice," said Kanse. "This shows that the FSAP-gene is important for protecting the brain."
The next step in the research demonstrated administering FSAP to mice after the induction of a stroke significantly improved their outcomes. This led the researchers to a final test, adding FSAP to a standard post-stroke therapy known as TPA.
The only current approved pharmacological therapy for acute ischemic stroke is an infusion of TPA (tissue plasminogen activator), a drug designed to rapidly dissolve blood clots in the brain. TPA must be administered to patients within the first few hours of a stroke, and even then it is only effective in around one-third of patients.
In the mouse experiments the researchers found combining FSAP with TPA significantly improved stroke outcomes compared to giving the animals TPA alone. An accompanying study from the same research team described the development of a novel drug that can stimulate the body to produce FSAP.
According to Kanse, it will be easier to produce and administer this FSAP-stimulating drug than to manufacture FSAP specifically. Further preclinical work will be needed before this novel treatment moves to human trials.
"We now need more research to find out if triggering the production of active FSAP will work as a treatment for stroke or not," said Kanse. "Ideally, the diagnosis and treatment should start immediately in the ambulance itself."
The new study was published in The FASEB Journal.
Source: University of Oslo